Get access to all handy features included in the IVIS website
- Get unlimited access to books, proceedings and journals.
- Get access to a global catalogue of meetings, on-site and online courses, webinars and educational videos.
- Bookmark your favorite articles in My Library for future reading.
- Save future meetings and courses in My Calendar and My e-Learning.
- Ask authors questions and read what others have to say.
Biology and Medicine of Rats
Get access to all handy features included in the IVIS website
- Get unlimited access to books, proceedings and journals.
- Get access to a global catalogue of meetings, on-site and online courses, webinars and educational videos.
- Bookmark your favorite articles in My Library for future reading.
- Save future meetings and courses in My Calendar and My e-Learning.
- Ask authors questions and read what others have to say.
Read
Table of Contents
I. Introduction
A. History and Use in Research
B. Behavior
II. Biology
A. Anatomy
B. Reproductive Anatomy and Physiology
III. Husbandry and Management
A. Handling
B. Housing and Feeding
C. Blood Sampling and Substance Administration
D. Euthanasia
IV. Surgery and Anesthesia
A. Anesthesia and Analgesia
B. Surgery
C. Castration
D. Ovariohysterectomy
E. Removal of Mammary Neoplasms
V. Diseases and Medicine
A. Infectious diseases
1. Respiratory Disease
2. Sialodacryoadenitis Virus (SDAV)
3. Diarrhea
4. Tyzzer's Disease
5. Ectoparasites
6. Endoparasites
B. Noninfectious diseases
1. Barbering
2. Dermatitis
3. Conjunctivitis
4. Malocclusion
5. Mammary Fibroadenoma
6. Megaloglobus
7. Myocardial Disease
8. Nutritional Deficiencies
9. Renal Disease
10. Retinal Degeneration
11. Ringtail
12. Urinary Calculi
C. Zoonotic diseases
1. Allergic Disease
2. Hantaan Virus
3. Leptospirosis
4. Ornithonyssus bacoti
5. Rat Bite Fever
6. Ringworm
7. Rodentolepis (Hymenolepis) nana
8. Salmonellosis
VI. Acknowledgements
VII. Recommended Reading for the Practitioner and References
I. Introduction
A. History and Use in Research
"Rat" refers to a wide variety of small animals of the family Rodentia. They tend to have coarse fur in dull colors such as brown and black, hairless tails, and powerful incisors, with which they can gnaw through hard materials. Most rats seen in private practice and used in a laboratory setting today are domesticated Norway rats, Rattus norvegicus. This animal’s original natural habitat was the steppes of Asia, but at some point in the 1600s, conditions changed and the rat became commensal with man, spreading throughout the world [1].
The path to domestication for Norway rats probably began in France and England in the 1800s, in association with rat baiting. Rats were captured and held in large numbers for the sport of rat baiting, in which trained terriers were timed to see how long it took them to kill a certain number of rats in a pit. The albino mutation is relatively common in the general rat population, and these animals were probably set aside as a curiosity, and later for breeding and show purposes. Some rats may have found their way from those first rat fanciers into laboratories [2].
In the 1850s, rats made their initial appearance as laboratory animals. Norway rats are widely regarded as the first species to be domesticated for scientific purposes [2]. In the laboratory, they are used today to study human and animal physiology, basic neuroscience, genetics, infectious and inherited diseases, and many other scientific disciplines. Rats, like mice, are tolerant of continued inbreeding. There are many strains of inbred rats commonly available. This genetic homogeneity allows them to serve as models for many human conditions. Common inbred rat strains include the Brown Norway, Fischer, Lewis, and F344. Outbred stocks of rats are also available from commercial suppliers. With their genetic heterogeneity, they are thought to better mimic the diverse genetics of human populations. They are often used in toxicology and drug development work. Common outbred rats include Wistar, Long-Evans, and Sprague-Dawley. There are also many specialized strains of rats being bred for laboratory use, including consomic rats, which are rats of one strain that carry whole chromosomes from another strain and rats with spontaneous genetic mutations, such as athymic nude rats, and the various obese and diabetic rats. Rats are becoming the most important animal models in the study of diabetes, obesity, and hypertension. Researchers found manipulating the rat embryo more difficult than the mouse embryo, so rats have lagged behind in the transgenics race. However, those difficulties have been conquered and transgenic rats are being created in ever greater numbers.
Today, rat fanciers abound, with hobbyists breeding rats for show and sale. These fancy rats are kept as pets and bred for many coat colors and varieties of pelage as well as characteristics such as large ears or short tails. There are numerous "ratteries" in every urban area in the United States, and there are rat fanciers’ associations in North America, Europe, Japan, and Australia. Despite the prejudice associated with their well-deserved reputation as economic pests and carriers of disease, domesticated rats can make fine pets. Some of the wild rat species are occasionally kept as pets, but this is not recommended (e.g., the recent monkeypox outbreak in the United States), and these species will not be addressed.
B. Behavior
Rats are curious, intelligent creatures that exhibit a wide variety of behaviors. They tend to be docile, showing aggression only in defense of their young. Some strains, however, are more aggressive than others. Rats can be trained to perform certain behaviors through the use of positive reinforcement. Some common behaviors in rats include standing (rearing up on their hind limbs), which is used to explore the environment, wrestling, which is a form of play in young rats, and grooming. Rats are not as neophobic as some rodents and will readily interact with new objects placed in their environment. Some objects suitable as toys for rats include Nylabones, PVC pipe, running wheels, and manipulanda, such as marbles or nuts and bolts. As with most rodents, however, rats find the presence of a conspecific more enriching than any toy. Rats are social animals and should not be housed singly if at all possible. If toys are used in the laboratory setting, they should be: approved by the Institutional Animal Care and Use Committee, suitable for the research being conducted, disposable or easily sanitized, and regularly examined for damage that could result in harm to the animals.
Rats may spend a good deal of their time standing. As quadrupeds, rats normally stand and move about on all four feet. In a bipedal standing posture, the animal may be stretched to its full length, with its hind legs extended, or may squat with its hind legs contracted beneath it, but its body held erect. The latter posture is the preferred posture for eating, drinking and grooming. Rats are nocturnal creatures, with their highest activity levels at night, but they are light sleepers, waking often during the day. A sleeping rat will tuck its head between its paws and its tail around its body. They often sleep huddled together in a corner of their cage or in a dark area, if one is provided. Rats may also sleep sprawled out on one side. Unlike mice, rats vary in their use of nesting material, with some strains and individuals making more use of such material than others. A pregnant or nursing female rat, however, will often take advantage of nesting material to prepare a nest for her pups.
Rats can hear into the ultrasonic range, and their vocalizations, especially those of young pups or aroused adults, extend into the ultrasonic range as well. Their hearing range at 70dB is 250 Hz to 70 kHz, with the most sensitive range from 8 - 32kHz. The ultrasonic portion of their communication is very important to the bonding of mother to young. When young rats are outside of the nest, they may squeak surprisingly loudly. This squeak has a large ultrasonic component, which alerts adult rats to their whereabouts. Rats will squeak and squeal when aroused or disturbed. They may also purr or chirrup, both of which usually indicate contentment.
Pheromones are an important part of the rat communication repertoire. These are transmitted through urine, sebaceous glands, and fecal matter. Using these pheromones, rats recognize kinship, social status, and sexual receptivity. Rats also respond to alarm pheromones from other rats [3].
II. Biology
A. Anatomy
The average life span of the domestic rat is 2.5 - 3.5 years. Exceptional members have been recorded at 5 years, but this is uncommon. An adult female rat reaches 250 - 300 g body weight at adulthood (higher during pregnancy) and an adult male rat reaches 400 - 500 g adult body weight. A distinguishing feature of rodents, including rats, is the absence of canines and the presence of prominent incisors. Rats are monophydontic, meaning they grow one set of teeth in their lifetime. The enamel of the rodent incisor contains iron, which gives it its yellow-orange color and its hardness Fig. 1. These incisors grow continuously and must be worn down through gnawing. The molars are also open-rooted, but they wear on each other, and are only rarely misaligned. The dental formula of the rat is 2(1/1 0/0 0/0 3/3) = 16 and the vertebral formula is C7 T13 L6 S4 Cd 27-30.
Figure 1. Normal rat dentition. Note the yellowish incisors and sharp gnawing surface.
Rats are mammals and as such, possess many similarities with other mammals. Only the peculiarities of the rat’s anatomy are addressed. For clinical pathology and other normative biological data, please see Table 1, Table 2, Table 3, Table 4, Table 5 and Table 6. A rat’s esophagus is lined entirely with keratinized epithelium. The stomach of the rat contains both a non-glandular and glandular portion, which are separated by the limiting ridge. The esophagus enters the stomach through a fold in the limiting ridge and this anatomic feature prevents rats from vomiting. The small intestine of rats is unremarkable, but rats possess a prominent cecum, which occupies much of their abdominal cavity. The rat has a four-lobed liver with no gall bladder. The pancreas is diffuse. The inguinal canals remain open throughout life.
Table 1. Normal physiological data for the rat [8,9]. As with all "normal" values, these values and the values presented in the other tables in this work, may not represent the mean or range for certain populations or strains of animals. For this reason, the values should be interpreted as approximations. | |
Life expectancy | 2.5 - 3.5 years |
Body weight - male | 300 - 500 grams |
Body weight - female | 250 - 350 grams |
Body temperature | 36.0 - 37.5°C (96.5 - 99.5°F) |
Daily food consumption (adult) | 5 g/100 g BW |
Daily water consumption (adult) | 8 - 10 ml/100 g body weight |
Daily urine production | 5 - 6 ml/6 ml body weight |
Urine pH | 7.3 - 8.5 |
Urine specific gravity | 1.04 - 1.07 |
Daily fecal production | 10 - 15 grams |
Table 2. Normal respiratory parameters for the rat [8,9]. | |
Respiratory rate | 70 - 110 breaths/min |
Tidal volume | 0.5 - 2.0 ml |
Minute ventilation | 75 - 130 ml/min |
Trachea diameter | 1.6 - 7.7 mm |
Alveolar surface area (400 gram rat) | 7.5 m3 |
Total lung capacity | 11.3 +/- 1.4 ml |
Vital capacity | 8.4 +/- 1.7 ml |
Functional residual capacity | 3.9 +/- 0.8 ml |
Residual volume | 2.9 +/- 1.0 ml |
Table 3. Normal cardiovascular parameters for the rat [8,9]. | |
Heart rate | 250 - 500 beats/min |
Mean systolic arterial blood pressure | 116 mm Hg |
Mean diastolic arterial blood pressure | 90 mm Hg |
Cardiac output | 50 ml/min |
Blood volume | 6 ml/100 gram body weight |
Sample volume | 2 - 4 ml |
Sample site | Lateral tail vein; saphenous vein |
pO2 | 93.2 mm Hg |
pCO2 | 39.9 mm Hg |
Arterial blood pH | 7.41 |
H+ | 38.6 +/- 0.6 nM |
Base excess | +1.8 +/- 0.4 |
Table 4. Normal serum biochemistry values for the rat [21]. For a more exhaustive list, including hormones, the reader is referred to Kohn and Clifford [9]. | |
Glucose (mg/dl) | 85 - 132 |
Urea nitrogen (mg/dl) | 32 - 54 |
Cholesterol (mg/dl) | 46 - 92 |
Total protein (g/dl) | 6.3 - 8.6 |
Albumin (g/dl) | 3.3 - 4.9 |
Globulin (g/dl) | 2.4 - 3.9 |
Aspartate aminotransferase (U/L) | 39 - 92 |
Alanine aminotransferase (U/L) | 17 - 50 |
Alkaline phosphatase (U/L) | 39 - 216 |
Sodium (mEq/L) | 141 - 150 |
Potassium (mEq/L) | 5.2 - 7.8 |
Chloride (mEq/L) | 99 - 114 |
Phosphorus (mg/dl) | 6.2 - 11.7 |
Calcium (mg/dl) | 10.7 - 13.7 |
Magnesium (mg/dl) | 2.6 - 3.11 |
Table 5. Normal hematology values for the rat [21]. | |
Red blood cells (x 10 ul) | 5.4 - 8.5 |
Hemoglobin (g/dl) | 11.5 - 16.0 |
Hematocrit (%) | 37 - 49 |
Platelets (x 10 ul) | 450 - 885 |
White blood cells (x 10 ul) | 4.0 - 10.2 |
Neutrophils (x 10 ul) | 1.3 - 3.6 |
Lymphocytes (x 10 ul) | 5.6 - 8.3 |
Total blood volume (ml/kg) | 50 - 65 |
The rat’s lungs are immature at birth and lack alveoli, alveolar ducts, and respiratory bronchioles. Remodeling occurs 4 - 7 days after birth and respiratory bronchioles are found 10 days after birth. The right lung of the rat has four lobes, while the left has one. The rat’s pulmonary veins contain cardiac muscle fibers.
Rats have several unique glandular structures. Steno’s gland (lateral nasal gland) is located in the maxillary sinus and it both humidifies air and controls mucus viscosity. Paired Zymbal’s glands (sebaceous glands) are found at the base of each ear. They are auditory sebaceous glands that open into the external ear canal. Rats also have Harderian glands (lacrimal glands), which secrete porphyrin, behind each eye. Secretions from these glands usually go unnoticed unless the rat is ill or stressed. Then, reddish-brown secretions may be seen rimming the eye or at the external nares. Front paws may also show staining as the animal grooms the irritating secretions away. These secretions resemble blood, but porphyrin fluoresces under ultraviolet light while blood does not.
Like other rodents, rats do not have many physiologic mechanisms to allow them to cope with heat. They cannot sweat and they cannot pant. Some heat is dissipated through vasodilation in the tail. Although increased salivation is seen as a response to overheating, rats will not drink more water in response to increased temperature. They will take saliva and spread it on their heads and bodies in attempts to cool themselves. Rats also thermoregulate through behavioral means such as burrowing and seeking shade.
B. Reproductive Anatomy and Physiology
A summary of rat reproductive norms may be found in Table 6. Male rats reach puberty at 40 - 60 days of age. Descent of the testes usually occurs between days 30 - 60. Sperm counts vary by strain [4]. The male rat has an os penis. Male rats have the following accessory sexual organs: ampulla, seminal vesicles, prostate, bulbourethral glands, coagulating glands, and preputial glands. The coagulating gland and prostatic and vesicular secretions are responsible for the copulation plug, a firm plug deposited in the vagina of the female after copulation. (This plug, when found outside the female rat, is capsule-shaped and approximately 5 mm long.) The male rat has no nipples. The adult male rat has a prominent scrotum and a longer anogenital distance than the female rat.
Table 6. Normal reproductive parameters for the rat [8]. | |
Sexual maturity | 50 +/- 10 days |
Gestation | 21 - 23 days |
Litter size | 8 - 14 |
Birth weight | 5 - 6 grams |
Eyes open | 10 - 12 days |
Ears open | 12 - 14 days |
Weaning | 21 days |
Chromosome number (diploid) | 42 |
Young female rats are born with a vaginal closure membrane, called the vaginal plate. This spontaneously ruptures before puberty (usually at 33 - 42 days of age), but may persist, resulting in a vagina and uterus distended with mucus and other secretions. Female rats reach puberty at 40 - 60 days of age (approximately 6 - 8 weeks). The female rat is a polyestrus spontaneous ovulator who cycles every 4 - 5 days. The rat is in proestrus for approximately 12 hours, estrus for approximately 12 hours, metestrus for approximately 21 hours, and diestrus for the longest portion of the cycle, approximately 55 hours. Rat estrus cycles can be evaluated through the use of vaginal smears. Vaginal cytology is similar to that of other animals in that a vaginal smear containing mainly cornified epithelial cells is a good indication of estrus. Ovulation usually occurs in the middle of the dark portion of the light/dark cycle. Rats are sensitive to changes in the light cycle, with continuous light readily producing persistent estrus due to polycystic ovaries [5].
The gestation period of the rat is 21 - 23 days and there is a fertile postpartum estrus. The female rat has 6 pairs of mammary glands and gives birth to an average of 10 - 12 pups. Cannibalism is uncommon, but does occur. It is a natural way for a dam to rid the nest of weak or ill pups, or may be precipitated by stress, especially in a first-time mother. Rat pups weigh 5 - 6 grams at birth, and are born blind, deaf, and hairless. Their ears open at approximately 12 days and their eyes between days 10 - 12. Rat pups are dependent on the female for their nutritional needs until they are approximately 14 days old. Once they are mobile, they may explore food if it is present in the bottom of their cage, but will still receive most of their calories from milk. During the early food exploration period, young rats may be observed engaged in coprophagy. This is a normal means of obtaining gut flora and exploring their environment. Most rats are weaned at 21 days of age. Weaning is usually performed by removing the animals from the home cage and separating the animals into single-sex groups. Animals from multiple litters may be mixed together at weaning. Animals may be housed at higher densities when smaller and separated as they become larger.
Rats may be housed in single-sex groups, in monogamous breeding situations, or in polygamous breeding situations. Male rats tolerate the company of other males quite well and may be housed together in single-sex groups. If breeding rats, the monogamous configuration allows for absolute knowledge of both maternity and paternity. Housing a male with more than one female allows for sure knowledge of paternity, but maternity may be confusing. Female rats will gang-nurse litters, and male rats will participate in care of the young. Housing more than one male with a group of females will result in fighting between the males.
III. Husbandry and Management
A. Handling
Although generally docile creatures, rats may object strenuously to being handled inappropriately. If attempting any restraint procedure for the first time, it is best to practice on a very young rat or a rat-sized stuffed animal. Larger or heavier rats do not enjoy being handled by their scruff or dorsal skin and will usually object with loud squeals and attempts to bite or escape. Young, docile rats may be handled by the scruff for minor procedures (Fig. 2). The best way to remove a rat from a cage for an exam is to gently grasp it close to the base of the tail and lift it from the cage. The rat should not be dangled by the tail or lifted by the tip of the tail, as tail slip (degloving of the skin), necessitating tail amputation, may occur. After lifting, the rat should be brought to the other forearm and placed there, with a hand remaining on the rat’s tail. This is an acceptable way to carry a rat for short distances (Fig. 3).
Figure 2. Scruffing a rat for restraint purposes.
Figure 3. Acceptable placement for carrying a rat for short distances. Notice how the handler has the rat firmly by the base of the tail.
Alternatively, the rat can be placed on a solid surface, such as a tabletop, for further manipulations. For minor manipulations, the rat may be restrained by hand. The rat is placed on a flat surface and the tail is grasped in one hand. The other hand is positioned over the rat’s shoulder blades. The restraining hand reaches down and using the thumb and forefingers, firmly grasps the rat around the thorax, behind (or underneath) the rat’s axillary area. This results in a rat with its arms lifted and pushed gently so they are lifted or crossed in front (Fig. 4). Care must be taken to not limit the rat’s breathing by restraining the rat too tightly. The restrainer’s other hand is free to perform a procedure or gently restrain the hind feet and tail. This posture will keep the rat’s teeth safely away from the restrainer and/or the person performing the procedure.
Figure 4. Restraint of a rat by grasping it around the thorax.
For more painful procedures, full-body restraint of the rat is recommended. A surgical towel makes an excellent rat restraint device. Many fractious rats become much calmer when shielded from the bright lights of an exam area by a dark towel. The rat can be wrapped in the towel, much like a cat may be wrapped in a towel, and relevant parts exposed for examination or manipulation. Alternatively, the rat can be shepherded into a small plastic bag with a corner cut off to allow the rat to breathe. (These bags are also commercially available.) The corner should be large enough to allow the rat to poke his muzzle out, but not his whole head. The rat is encouraged to enter the bag. This method of restraint is stressful to the rat and may cause overheating. It should only be used for short periods of time for procedures like intraperitoneal injection. If a practice or laboratory sees a large number of rats, the purchase of a commercial rat restraint may be valuable. It is a clear plastic cylinder; some have a flattened side (for easier use) with adjustable closing pieces that fit over the tail (Fig. 5). The advantages of these restraints are that the rats are much more comfortable than in a plastic bag, they may be held longer in the restraint without fear of overheating, and they provide easy access to the tail and paws. The disadvantages are that they are more expensive than surgical towels or plastic bags, they must be sized exactly to the rat (and some rats are much too large to ever fit a commercial restraint), and they often do not allow good access to the abdomen or limbs.
Figure 5. Commercially available rat restraint.
B. Housing and Feeding
Rats may be housed in a variety of cages and on a variety of surfaces. Solid-bottomed and wire-bottomed cages are the most common, with wire usually used in situations where there are large numbers of animals housed together, or where it is important that the rat not have access to its own fecal matter. Wire-bottom cages are unsuitable for breeding, as the wire may injure the young pups. Foot lesions, while still uncommon, are more common in rats housed on wire-bottomed cages. Foot lesions are more likely in older, heavier animals that have been housed on wire for over a year [6]. Many institutions are now providing resting areas for animals that must be kept in wire-bottomed cages. The animals will not soil their sleeping areas if given the chance, and the addition of a small platform or solid area allows the animals to rest off the wire, further reducing the chance of foot lesions. Animals housed in a wire-bottomed cage may need the litter beneath their cage changed less frequently than animals housed in solid-bottomed cages. Since the animals are not directly exposed to the litter, any litter is acceptable, as long as it allows for absorption of urine.
Most solid bottom cages are made from plastics, specifically polycarbonate or polypropylene. If animals are housed in a solid-bottomed cage, the choice of bedding becomes more important, as animals will eat, sleep, and play in this material. Cedar or other aromatic woods will induce hepatic enzymes and may cause irritation to mucous membranes. Chipped hardwood or heat-treated pine bedding is acceptable, as is any commercially available paper product bedding, such as Alpha-Dritm or CareFreshtm. Nude rats may develop conjunctivitis from the dust from some paper product beddings. This should be monitored carefully, or nude rats should be kept on shavings. Newspaper is not a good choice, but unprinted newsprint will do, although it is not ideal. Litter should be changed when it appears soiled. This may be as infrequently as once weekly or as frequently as every day, depending on the housing density. Ideally, cages should be sanitized at least once weekly. Different countries may have different recommendations for housing densities or cage size. In the United States, The Guide for the Care and Use of Laboratory Animals outlines acceptable housing densities for rats of various sizes. That information is presented in Table 7.
Table 7. Recommended minimum cage sizes for rats [19]. | ||
Weight of rat | Floor area (cm2) | Height (cm) |
Less than 100 g | 110 | 18 |
Up to 200 g | 148 | 18 |
Up to 300 g | 187 | 18 |
Up to 400 g | 258 | 18 |
Up to 500 g | 387 | 18 |
Greater than 500 g | ≥452 | 18 |
Fresh, clean water should be available at all times to rats. Water is best provided using a glass or plastic bottle equipped with a sipper tube, or through an automatic watering system. Dishes of open water will be quickly dirtied or overturned. Rats should be fed a hard, pelleted diet designed for use in rodent species. With their constantly growing incisors, a pelleted feed provides a hard gnawing surface that prevents incisor overgrowth. Rat blocks are available in many formulations and some companies will incorporate a desired substance, such as hormones or antibiotics, into the feed. The nutrient requirements of rats are available in print [7-9]. Rats fed ad libitumtend to become extremely fat, especially when kept for long periods of time. Once the rat has reached adulthood, limiting the amount of food available decreases weight gain and encourages longevity [10]. Treats should be limited for pet rats. Depending on the health status of the facility and the experimental status of the animal, treats may be a part of the laboratory rat’s diet. Laboratory-appropriate treats are available from feed companies. The use of home-formulated treats is not recommended in a laboratory setting.
In the animal facility, 10 - 15 air changes per hour are necessary to dissipate the heat load and environmental CO2 and NH3 production of animals. Rats acclimate well to a light cycle of 12 hours of light and 12 of darkness. If better breeding performance is desired, moving to 14 hours of light a day may increase fertility, as rats are long-day breeders. Albino rats may show retinal degeneration with exposure to bright lights, so this should be minimized. Temperature and humidity should be controlled for the comfort and safety of the rats. As mentioned earlier, rats do not thermoregulate well and are prone to hyperthermia. Recommended temperatures are 21 - 24°C and humidity should be kept between 30 - 70% if possible. Nude or hairless rats may be kept at a slightly warmer temperature.
C. Blood Sampling and Substance Administration
The most common means of administration of substances in the rat are intraperitoneally, intravenously, and per os, through oral gavage or administration in feed or water. The lateral tail veins in the rat are large enough to allow for both administration of drugs or compounds and withdrawal of blood. Blood may also be obtained from the jugular veins, the lateral saphenous veins, and the orbital plexus. The use of the orbital plexus for blood sampling should only be conducted on anesthetized animals. As a rough guide, no more than 1% of the animal’s body weight should be taken during a single blood collection. For example, in a 300 g rat, the total blood volume is approximately 6% of its body weight, or 18 ml One percent of the body weight is 3 ml Intraperitoneal (IP) injections should be made into the lower left quadrant of the abdomen (Fig. 6). Maximum injection volume for the IP route is approximately 10 ml Intramuscular (IM) injections should be made into the quadriceps muscle. As this muscle is quite small, the maximum injection volume should be 0.2 ml, Intravenous (IV) injections may be performed in the lateral veins of the tail (Fig. 7), IV injection volumes over a short period should not exceed 2 ml, but if given slowly, up to 3 ml may be given at one time. When giving IV injections in the rat, the small size of the vein makes drawing back to ensure placement ill-advised. A blood flash is rarely seen in the needle hub. A small amount of substance should be injected before injecting the entire volume. If the tail vein blanches, then the substance is placed intravenously.
Figure 6. Acceptable site for IP injection in the rat. A strict midline injection runs the risk of puncturing the bladder or other structures.
Figure 7. Lateral tail vein. If the injection attempt is begun caudally, the vein is closer to the surface and easier to access.
Subcutaneous (SQ) injections are best performed along the skin of the flanks or back. If animals are to be handled by the scruff, injecting in that area is not recommended. SQ injection volumes may be up to 5 ml in larger rats. Per os (PO) administration of known volumes of substances in the rat is best accomplished through oral gavage. Volumes of up to 5 ml may be administered via gavage. Gavage in the rat is usually performed using a 15 or 16 gauge rigid metal gavage (or feeding) needle. These needles have differently-sized bulbs at the tip, with smaller animals (under 75 g) using a 2 mm bulb and larger animals (over 180 g) needing a 4 mm bulb. When accustomed to the procedure, rats do not object to gavage. Care must be taken to avoid administering substances intratracheally. This is best accomplished by measuring the distance to the stomach on the outside of the rat before attempting gavage, passing the needle to one side of the mouth (not centrally), and watching the rat carefully for signs of trouble, such as struggling or injection solution appearing in the nose or mouth. In many cases, animals may be trained to take oral formulations of drugs through being allowed to lick the formulation from a syringe.
If an approximate dose of a compound to be given PO is acceptable, substances may be administered in the feed, water, or in sweet-tasting treats. Although administration of drugs via water bottle is a commonly-performed practice, it can have several pitfalls. In most cases, animals will initially reject the strange-tasting water, resulting in animals that not only need treatment for a disease, but are now dehydrated. Some substances must be handled in certain ways (e.g., tetracycline should be administered in a 5% sucrose solution for palatability, and the solution must be protected from light), and the length of time that compounds remain active in aqueous solution may not be known. In addition, the animals will receive a dose based on the amount of water they drink, not based on their weight or their need for the drug. This may prove problematic when treating for diseases such as pinworms. Smaller animals may not be able to drink enough water to achieve an effective dose. The same problems arise when compounds are administered via incorporation into feed. These routes should only be used when the safety and efficacy of the compound is known and economies of scale make it the most effective choice.
D. Euthanasia
In the 2000 Report of the American Veterinary Medical Association Panel on Euthanasia [11], several methods of euthanasia are listed as acceptable for use in laboratory rodents. Rats may be euthanized through inhalation of carbon dioxide, overdose of inhalant anesthetics, or overdose of barbiturates, either IV or IP. In a practice setting, there is very little call for the use of the conditionally acceptable methods of decapitation and cervical dislocation. If cervical dislocation must be used, it is best performed on rats under 100 grams. Larger rats are too muscular and will resist the procedure, resulting in injury and distress to the rat and probably the handler.
IV. Surgery and Anesthesia
A. Anesthesia and Analgesia
Fasting the rat before anesthetic administration is not necessary. Rats are unable to vomit, which limits the risk of aspiration pneumonia and have a high basal metabolic rate, which means they need to eat quite often. If rats must be fasted for intestinal surgery, it is not necessary to fast longer than six hours. Metabolic support may be provided through the use of sugar water [12]. Never water restrict a rat, as the effects of dehydration can be severe. Rats may be anesthetized using injectable agents, or masked or intubated for the use of inhalant anesthetic agents. Injectable agents work quite well for most rat procedures. Masking a rat down is not recommended, but induction in a box usually proceeds quite smoothly. If intubation is desired for a longer procedure, the use of a 14 - 20 gauge catheter as an endotracheal tube, an otoscope, and a guide wire will facilitate that procedure. Place the rat in dorsal recumbency and open the mouth. Use the otoscope to visualize the larynx and place the guide wire in the trachea. Keep the wire in place while removing the otoscope. Thread the catheter over the guide wire and then carefully remove the guide wire. Tie the catheter, using the hub, to the lower jaw. Attach the catheter to the anesthetic machine. Due to the small tidal volume of the rat, minimization of dead space in the anesthetic circuit is extremely important.
Analgesic agents are best administered to the rat through injections. The dose may be more precisely controlled in that fashion, and the effects evaluated. Rats in pain exhibit certain characteristic behaviors. These include abdominal writhing, falling or staggering when attempting to move, remaining hunched in the cage, and back arching [13]. Evaluation of rats for these clinical signs postoperatively may indicate a need for more than perioperative analgesia. Since rats cannot vomit, nausea in rats is evinced by pica. This behavior can be injurious to the rat. Monitor rats receiving opioids closely for this behavior. Buprenorphine, although widely available, may not be suitable for use in rats as it is known to cause pica in some strains of rats, most notably Sprague-Dawley rats [14]. See Table 8 for a formulary, including dosages for anesthetic and analgesic agents.
Table 8a. Formulary: Sedation and anesthesia [8,21-26]. | |
Agent | Dosage |
Ketamine | 50 - 100 mg/kg IM, IP |
Xylazine | 1 - 5 mg/kg IM, IP |
Medetomidine | 0.1 - 0.5 mg/kg IP, SQ |
Acepromazine | 2.5 mg/kg IM, IP |
Atropine | 0.05 mg/kg IP, SC |
Diazepam | 2.5 - 5.0 mg/kg IP, IM |
Midazolam | >5 mg/kg IP |
Fentanyl/Droperidol | 0.5 ml/kg IM |
Pentobarbital | 40 - 50 mg/kg IP, IV |
Halothane | Induction: 3 - 4%, Maintenance: 1 - 2% |
Isoflurane | Induction: 3 - 4%, Maintenance: 1.5 - 3% |
Table 8b. Formulary: Injectable anesthetic cocktails [8,21-26]. | ||||
Depth and duration of anesthesia | Agent | Dosage | Agent | Dosage |
Surgical, 20 - 30 minutes | Ketamine | 75 mg/kg | Medetomidine | 0.5 mg/kg |
Surgical, 20 - 30 minutes | Ketamine | 75 - 100 mg/kg | Xylazine | 10 mg/kg |
Light, 20 - 30 minutes | Ketamine | 75 mg/kg | Acepromazine | 2.5 mg/kg |
Light, 20 - 30 minutes | Ketamine | 75 mg/kg | Diazepam | 5 mg/kg |
Light, 20 - 30 minutes | Ketamine | 75 mg/kg | Midazolam | 5 mg/kg |
Table 8c. Formulary: Injectable agent antagonists [8,21-26]. | ||
Agent | Antagonist | Dosage |
Fentanyl | Butorphanol | 0.4 mg/kg SQ |
Fentanyl | Naloxone | 0.01 - 0.1 mg/kg IV, IM, IP |
Xylazine, Medetomidine | Atipamizole | 1 mg/kg SQ |
None specifically | Doxapram | 5 - 10 mg/kg IM, IV, IP |
Table 8d. Formulary: Analgesia [8,21-26]. | |
Agent | Dosage |
Acetaminophen | 110 - 305 mg/kg IP, PO |
Aspirin | 100 mg/kg PO |
Buprenorphine* | 0.05 - 0.10 mg/kg SC, IV BID |
Butorphanol | 2 mg/kg SC q 4 hours |
Carprofen | 5 mg/kg SC |
Flunixin meglumine | 2.5 mg/kg SC, IM BID |
Ketoprofen | 5 mg/kg SC |
Morphine | 2.5 mg/kg SC q 2 - 4 hours 1 - 4 mg/kg IV q 2 - 4 hours |
* May cause pica in some strains of rat. |
Table 8e. Formulary: Anti-infective agents [8,21-26]. | |
Agent | Dosage |
Ampicillin | 20 - 100 mg/kg daily or TID; PO,SC |
Cephalexin | 15 mg/kg SC; 60 mg/kg PO |
Chloramphenicol palmitate | 50 - 200 mg/kg TID; PO |
Enrofloxacin | 2.5 - 10 mg/kg BID; PO or 10 mg/kg BID SQ |
Doxycycline | 2.5 mg/kg BID; PO |
Fenbendazole | 20 mg/kg daily x 5 d; PO |
Griseofulvin | 1.5% (15 mg/ml) DMSO solution, topically, 5 - 7 d |
Ivermectin | 200 - 400 µg/kg; PO, SC repeat in 8 - 10 d For topical administration, dilute 1:100 in equal parts water and propylene glycol. Place several drops between scapulae. |
Metronidazole | 20 - 60 mg/kg BID or TID, PO 1 ml of oral preparation in 150 ml drinking water * |
Penicillin G | 40,000 - 60,000 IU/kg BID, SQ, IM |
Praziquantel | 5 - 10 mg/kg; PO, SC, IM repeat in 10 d |
Tetracycline | 100 mg/kg SC (high dose); 5 mg/kg PO in drinking water** |
Trimethoprim-sulfadiazine | 30 mg/kg BID-daily; SC, PO |
*Rats may not tolerate the taste of metronidazole in their drinking water. **Water may need to be sweetened with 5% sucrose. Water bottle should be protected from light and changed daily. |
B. Surgery
In the laboratory setting, the most common surgery performed on rats is cannulation of the jugular veins. In practice, rats may be castrated or spayed, and removal of mammary neoplasms in aged female rats is another common surgery. Suture material used in rats is generally 4 - 0 or smaller. Rats do not tolerate skin sutures well, so all surgical closures should be accomplished with tissue glue, surgical staples, or subcuticular closures. E-collars for rats and other small mammals are commercially available, or they may be made for the rat using tape and radiography film.
Surgical support is critical in the rat. Due to their small size and high metabolic rate, they lose heat rapidly. Warming is best accomplished through the use of recirculating water heating pads, but may also be accomplished using commercially available "hand warmers" or surgical gloves filled with hot water. Care should be taken to avoid thermal damage to the skin, regardless of the method used. Warm fluids may also be administered subcutaneously. During recovery, animals should be kept warm and quiet. Since rats are exophthalmic, their eyes quickly become dry during surgery. The use of eye lubricants during the surgical and postoperative period is important. Injectable anesthetic agents used in rats often have prolonged sleep times, which means that animals may be asleep or groggy for over two hours. It is best if they are not allowed to recover on loose bedding, since they may scratch their corneas or inhale or ingest particulate matter. Animals should not be placed back into their cage or pen until they show signs of recovery.
C. Castration
(orchiectomy) is accomplished in the rat in the following manner: Place the anesthetized rat in dorsal recumbency. Prepare the scrotum using standard surgical scrub techniques. Make a small (1 cm) median incision at the distal tip of the scrotum. Clear the subcutaneous connective tissue, and then visualize the testes. If they are not readily apparent at the incision site, apply gentle pressure to the lower abdomen to force them into the scrotum. Incise the muscular sac of the testes and expose them by gently pulling on the cauda epididymis. Ligate the blood vessels and the vas deferens and remove the testis and epididymis. Close the muscular sac with a suture, and close the skin with a wound clip. If an open technique is preferred, the surgeon may close the inguinal rings. Closure is not necessary, however, as intra-abdominal fat seems to prevent the formation of scrotal hernias.
D. Ovario-hysterectomy
in the rat is performed through a ventral midline incision. The abdomen is prepared in the standard manner. The abdominal musculature and peritoneum are incised and the bicornuate uterus is visualized. The utero-ovarian artery is ligated and the uterine vessels are ligated again immediately before the collateral blood supply to the cervix. The uterus and ovaries are removed and the abdomen is closed in two layers, with the skin closed preferably with wound clips.
E. Removal of Mammary Neoplasms
in the rat is often a matter of the removal of an uncomplicated space-occupying mass. They are usually fibroadenomas, so will often shell out of the skin easily. Since the masses may be allowed to become quite large before removal is considered, closure of dead space caused by the removal of the mass will be a consideration. In addition, removal of the mass may remove a significant amount of blood and fluid from the rat. Fluid support of the blood volume should be addressed if necessary.
For a more detailed treatment of survival surgery in small rodents, please see the companion chapters in this volume: Principles of Aseptic Rodent Survival Surgery: General Training in Rodent Survival Surgery - Part I and Principles of Aseptic Rodent Survival Surgery: General Training in Rodent Survival Surgery - Part II by P. A. Brown and S. Hoogstraten-Miller.
V. Diseases and Medicine
Infectious diseases in rats are often clinically silent. Weanlings and sucklings are most likely to show clinical manifestations of disease processes. Often, evidence of many viruses known to infect rats is only detectable via serological testing, usually by ELISA. See Table 9for a list of agents for which research institutions and commercial rodent vendors commonly screen animals. Readers of this chapter who work with laboratory animal facilities will be well-served by perusing the chapter in this book on Quality Assurance/Surveillance Monitoring Programs for Rodent Colonies by J. D. Reuter and R. C. Dysko. Practitioners can find commercial diagnostic laboratories that perform screening tests for these diseases on the Internet or by contacting a local research university. In most cases, however, screening pet rats for this "laundry list" of diseases is unnecessary. Most disease entities or clinical problems observed by practitioners treating pet rats will likely be the result of accidents (trauma), husbandry-related deficiencies, or age-related changes. As noted above, very few of the diseases listed in Table 9 will produce clinical signs. With regard to specific health conditions, skin problems, gastrointestinal illnesses, and respiratory ailments are the most commonly seen. Some conditions related to unique anatomic characteristics of the rat may also arise. Vaccinations are not normally given to rats and none are currently approved for use in rodents. However, antibiotics and anthelmintics can be given safely to rodents. A formulary for rats is provided in Table 8.
Table 9. List of infectious agents for which research institutions and commercial vendors commonly screen. | ||
Viruses | Bacteria | Parasites |
Sendai virus | Mycoplasma pulmonis | Encephalitozoon cuniculi |
Pneumonia virus of mice | Cilia-associated respiratory bacillus | Syphacia obvelata S. muris |
Rat coronavirus / sialodacryoadenitis virus | Corynebacterium kutscheri | Aspiculuris tetraptera |
Rat parvovirus | Helicobacter hepaticus H. bilis | Hymenolepis (Rodentolepis) spp. |
Kilham rat virus | Salmonella spp. | Heterakis spumosa |
Toolan’s H-1 virus | Streptobacillus moniliformis | Trichuris muris |
Reovirus type 3 | Klebsiella pneumoniae K. oxytoca | Radfordia ensifera R. affinis |
Rat enterovirus | Pasteurella pneumotropica | Myobia musculi |
Lymphocytic choriomeningitis virus | Pseudomonas aeruginosa | Toxoplama gondii |
Hantavirus | Staphylococcus aureus | Polyplax spinulosa |
Mouse adenovirus | Streptococcus pneumoniae | Ornithonyssus spp. |
| Streptococcus spp., beta hemolytic and Lancefield Grp B,G, spp. | Trichosomoides crassicauda |
|
| Pneumocystis carinii |
|
| Enteromonas spp. |
|
| Coccidia spp. |
|
| Trichomonas spp. |
|
| Giardia spp. |
|
| Spironucleus muris |
|
| Hexamastix spp. |
|
| Entamoeba spp. |
A. Infectious Diseases
1. Respiratory Disease
Rats are prone to diseases of their respiratory tract. Rhinitis, bronchitis, and pneumonia can be attributed to one or more of several agents known to infect rats: Mycoplasma pulmonis, cilia-associated respiratory (CAR) bacillus, sialodacryoadenitis virus, and Sendai virus are four examples of agents that can cause respiratory illness in rats. Taken individually, these agents may produce only a mild respiratory illness. However, these agents often occur concurrently and the disease process is exacerbated. Pneumonia in rats is usually characterized by nonspecific signs, such as lethargy, weight loss, ungroomed hair coat, and dyspnea. Rats sometimes exhibit snuffling or "chattering", a word used to describe moist rales audible to the naked ear. Other agents known to complicate respiratory conditions in rats include Streptococcus pneumoniae, and Corynebacterium kutscheri. Supportive therapy is indicated, and treatment may include antibiotics such as enrofloxacin, tetracyclines, or cephalosporins. Rats ill with respiratory disease benefit from frequent cage changes which reduce high levels of ammonia in the environment.
2. Sialodacryoadenitis Virus (SDAV)
SDAV is a coronavirus affecting rats. Infection is often subclinical in weanling or older rats, but suckling animals will develop lower respiratory disease. The virus has a predilection for the salivary and lacrimal glands and affected animals often exhibit a range of dramatic clinical signs. These may include nasal discharge, blepharospasm, epiphora, and intermandibular swelling. As the infection resolves, the damaged tissues may take some time to become functional again. Reduced tear output in the post-infective period often results in ocular sequelae such as corneal ulcerations, glaucoma, and megaloglobus.
3. Diarrhea
Diarrhea is an uncommon finding in adult rats. However, suckling and weanling rats are prone to infections with several viruses and bacteria that may result in diarrhea. In a previously uninfected colony, infection of young animals with parvoviruses can cause diarrhea or steatorrhea, runted, jaundiced pups, and cerebellar hypoplasia. Although there are at least three different strains of parvovirus, only one, Kilham’s rat virus, is associated with clinical disease. Salmonella (see Zoonotic Disease section) and Tyzzer’s disease (see below) may also cause diarrhea in rats.
4. Tyzzer’s Disease
First discovered in 1917 by Tyzzer in Japanese Waltzing mice, this disease is caused by Clostridium piliforme, formerly known as Bacillus piliformis, a spore forming anaerobic bacterium. It is transmitted horizontally through the fecal-oral route. Animals that carry the bacterium are usually asymptomatic, but a clinical syndrome may be seen in recently weaned rats. Nonspecific signs such as anorexia, lethargy, emaciation, ruffled fur, or sudden death without clinical signs may be observed. Mucoid, bloody diarrhea may also be seen. On necropsy, animals may have megaileus. Many other organs, including liver, cecum, colon, and heart, can have characteristic pathologic lesions. Histopathologic observation of bacilli in target organs is diagnostic, and best obtained using a Warthin-Starry silver or Giemsa stain. There is no recommended treatment other than supportive care. Antibiotics effective against Clostridia spp. may be used.
5. Ectoparasites
Ectoparasites are common in rats. They are usually diagnosed via skin scraping or adhesive tape impression of the pelt. Mites such as Myobia musculi or Radfordia affinis are probably the most common ectoparasite in rats. Clinical signs may include alopecia and pruritis, although infections may be asymptomatic. Treatment is with ivermectin given subcutaneously, orally, or topically for two or three applications separated by 7 - 10 days. Fleas and lice may also be found on pet rats, but they are less common. The University of Missouri’s Research Animal Diagnostic Laboratory is an excellent source of photographs of the common endo- and ectoparasites of rodents and rabbits. Go to RADIL for a comprehensive list. In addition, Parasites of Laboratory Animals, by Dawn Owen, has a number of high-quality photographs of ecto- and endoparasites [15].
6. Endoparasites
Rats may host enteric parasites such as pinworms, Syphacia muris or Aspiculuris tetraptera, and less commonly, the rodent tapeworms, Rodentolepis (Hymenolepis) nana or Rodentolepis (Hymenolepis) diminuta. Pinworms, due to the environmental persistence of their ova, are a common problem in research institutions. Unless burdened with large numbers of parasites, there are no clinical signs. Mild enteritis or rectal prolapse could be symptoms of a severe infection. Diagnosis of Rodentolepis or Aspiculuris is by fecal flotation. Syphacia eggs are best seen using an adhesive tape impression of the rectal area. ivermectin or fenbendazole are commonly used effective treatments for pinworm infections. ivermectin may be administered topically, via subcutaneous injection, or in drinking water. Fenbendazole is best administered as part of a food pellet. Effective treatment regimens for laboratory facilities usually involve either continuous feeding or two-week on/two-week off 6 - 12 week regimens of anthelmintics, coupled with a rigorous environmental decontamination after the first treatment. Piperazine, although less effective than either ivermectin or fenbendazole, may also be administered in drinking water at a rate of 2 g/L [16]. Hemobartonella muris is an uncommon bacterial parasite that affects the red blood cells of rats. It is transmitted by the spiny rat louse, Polyplax spinulosa and can cause anemia, weight loss, and dyspnea.
B. Noninfectious Diseases
1. Barbering
Patterned hair loss may be observed occasionally in group-housed rats. A dominant rat may chew the hair or whiskers of the subordinate rat(s). The skin beneath the barbered hair is usually normal, and the dominant animal may be identified as the only animal in the cage with no missing hair. Removing the dominant animal usually does little to correct the problem, as another dominant animal may assume the behavior.
2. Dermatitis
Rats will typically spend much of their time grooming and when healthy, maintain a smooth, clean, fully haired coat. Patches of hair loss can arise from behavioral anomalies such as excessive grooming, rubbing, or hair plucking. Some aged or pregnant rats may also exhibit hair loss. Scratching or fighting may lead to wounds. These wounds are likely to become secondarily infected with a staphylococcal or streptococcal organism. Secondary infections can be treated with topical antibiotic ointments and clipping of the nails. E-collars may also aid in the treatment of dermatitis.
3. Conjunctivitis
Rats normally produce porphyrin-containing secretions from the Harderian gland (lacrimal gland), which is located behind the eye. These secretions lubricate the eye and from there, drain into the nose. The gland constantly produces fluids, but normal grooming removes them. When they are allowed to accumulate, they are sometimes mistaken for blood. The condition known as chromodacryorrhea or "red tears" can be seen when the porphyrin-containing lacrimations or nasal secretions accumulate around the eyes or nose. The appearance is not pathognomonic for any particular disease, but is often a sign of stress, dehydration, or general malaise. One specific agent often associated with conjunctivitis in rats is Pasteurella pneumotropica, which can be isolated from the nasopharynx, cecum, vagina, uterus, and conjunctiva. Pasteurella infection is usually asymptomatic. Enrofloxacin is effective against Pasteurella in some cases.
4. Malocclusion
Rat incisors are hypsodontic, or open rooted. They continue to grow throughout the life of the animal. When the teeth are not aligned for proper wear at the surface, they can grow to excessive lengths and cause significant trauma to the occlusive surface of the mouth and surrounding tissues (Fig. 8). This is usually a problem of the incisors, not the molars. Malocclusion can be inherited or be caused by trauma to the tooth root. Whenever a rat presents with anorexia or weight loss, the teeth should be examined first to see if they are misaligned. Animals with this condition should have their incisors checked every few weeks and trimmed, preferably with an electric burr to avoid loosening the teeth, which may occur if the teeth are clipped. Molars cannot be managed in this way, and an animal with maloccluded molars may need to be euthanized.
Figure 8. Malocclusion in a rat. Both the upper and lower incisors have continued to grow, resulting in circular teeth that, in the case of the upper incisors, pierce the palate.
5. Mammary Fibroadenoma
Tumors of the mammary glands are common in aged female rats. The majority of these are benign fibroadenomas that may ulcerate or cause mechanical interference with locomotion of the rat. These tumors can often be successfully removed surgically.
6. Megaloglobus
Megaloglobus is a pathologic enlargement of the globe of the eye of the rat due to various causes. These causes may include a genetic tendency to retain the pupillary membrane or a viral infection, specifically sialodacryoadenitis virus, a coronavirus. There is no known treatment, other than enucleation, for the condition, which is occasionally a finding in pets or research animals. It is generally believed that there is pain associated with the initial development of the condition as with some glaucoma-like diseases in humans. Rats have shallow eye sockets and normal handling of the rat may result in a distressing (to the handler) protrusion of the eyes. Normal handling will not proptose the eyeball, however.
7. Myocardial Disease
In rats, myocardial disease is sometimes referred to as cardiomyopathy and is a common cause of death in older rats. The heart is often enlarged, sometimes with pale streaks visible grossly. It is occasionally seen in animals less than six months of age. Sudden death is often the first and only clinical sign observed.
8. Nutritional Deficiencies
Balanced rodent chows are readily available from many commercial sources. However, improper storage of these diets can lead to degradation of minerals or vitamins that are sensitive to environmental temperature and humidity. Poor hair coat or reduced reproductive performance could reflect dietary imbalance and may be addressed by replacing outdated or spoiled feed.
9. Renal Disease
Hydronephrosis is often reported as an incidental finding in rats. It can vary from mild to severe dilation of the renal pelvis and may also affect the ureter. Chronic progressive nephropathy is a common age-related disease of the rat kidney and can be a cause of death in old rats. It is a progressive condition and usually more common in males than in females. Nephrocalcinosis is also observed in rats. It is more common in females, and can be found in animals as young as 7 weeks. It is characterized by the finding of calcium phosphate anywhere in the renal tissue, and can have an incidence as high as 50% in some strains of rats. Dietary restriction has been shown to reduce the incidence of renal disease as well as myocardial disease in rats [17].
10. Retinal Degeneration
Albino rats are susceptible to retinal degeneration when they are exposed to light levels above 130 - 270 lux [18]. Recommended room light levels are 325 - 400 lux when measured at one meter above the floor [19]. When in doubt, albino rats should be maintained at a distance from any direct light source, and the dark cycle of their photoperiod should be maintained.
11. Ringtail
Ringtail is an uncommon finding in the rat. It is characterized by annular constrictions of the tail compromising circulation and occasionally resulting in necrosis of distal portions of the tail. The cause is attributed to environmental factors such as low ambient humidity. Efforts to experimentally reproduce the condition have been unsuccessful. There is no known treatment. The condition is usually self-limiting, but amputation of necrotic portions of the tail may be necessary.
12. Urinary Calculi
Bladder stones are found in some older rats. The precise etiology is not well described, but genetics, imbalances in diet, and unsanitary environmental conditions have all been implicated in their development. Urinary tract infections exacerbated by wet or dirty bedding has also been linked to the formation of calculi. Calcium carbonate, struvite, carbonate-phosphate and magnesium stones have all been recovered from the urinary bladders of rats.
C. Zoonotic diseases
Rats in the wild may carry many diseases and parasites communicable to humans. Rats may carry plague-bearing fleas, typhus-bearing lice, or disease-bearing ticks. Like most small rodents, they are unlikely to carry rabies, however, being too small to survive the attack of a rabid animal. It is relatively rare to observe these conditions in laboratory or pet rats. Some zoonotic diseases that may be seen in captive rats are listed below. Check with your local public health authorities to determine if any of these diseases are reportable in your area.
1. Allergic Disease
Rodents and rabbits are highly allergenic to many people, especially those with underlying atopic disease. The allergenic proteins in rats are found in the urine. The protein, Rat n1, is a pheromone carrier and is found in higher levels in the urine of male rats [20].
2. Hantaan Virus
There are many descriptive terms applied to a group of rodent-borne diseases caused by several viruses of the Hantavirus group. In Southeast Asia, hantaviruses are associated with outbreaks of hemorrhagic and renal diseases. In June of 1993, a newly recognized hantavirus was identified as the etiological agent of an outbreak of severe respiratory illness, Hantavirus Pulmonary Syndrome (HPS), in the southwestern USA. It was contracted from exposure to deer mice. Cotton rats, Sigmodon hispidus, and the rice rat, Oryzomys palustris, found mostly in the southern USA, have been associated with hantaviruses that can cause illness and death in humans. Hantaviruses do not cause overt illness in their reservoir hosts. Infected rodents can shed virus in saliva, urine, and feces for variable time periods.
3. Leptospirosis
Leptospirosis is caused by the bacterium Leptospira interrogans. Hosts include rats, mice, moles, gerbils, rabbits, hamsters, cattle, and other mammals and reptiles. Leptospiral infections are rare in laboratory rats. The disease can vary in both humans and animals from inapparent to severe infections and death. Organisms can be carried and shed in the urine for long periods of time.
4. Ornithonyssus bacoti
O. bacoti is a mesostigmate mite, found rarely on laboratory rats. It is sometimes known as the tropical rat mite. Heavy infestations of this blood-sucking mite could lead to general poor health, anemia, decreased reproductive efficiency, and occasional deaths. It spends little time on the host so may be difficult to detect. In humans, the mite is associated with a pruritic rash.
5. Rat Bite Fever
This human disease is caused by Streptobacillus moniliformisor Spirillum minus,which are nonpathogenic commensals inhabiting the nasopharynx and respiratory tract of rats. These bacteria may also be present in the blood and urine of infected rats and may be transmitted to humans via aerosols, fomites, and the bite of infected rats. In humans, there is a 3-10 day incubation period and disease symptoms may include fever, vomiting, arthralgia, and rash. In humans, the disease is treated with antibiotics, usually penicillin. Carrier rats are often euthanized.
6. Ringworm
As in other animals, ringworm in rats may be diagnosed by fungal culture and Wood’s lamp examination. It is usually caused by Microsporum or Trichophyton spp. and can cause pruritis, alopecia, and scaling of the affected areas. Localized topical treatment with several available antifungal agents or iodophor antiseptics has been shown to be effective.
7. Rodentolepis (Hymenolepis) nana
This tapeworm is found in the small intestines of rats, mice, hamsters, and primates, including man. R. nana can have a direct or indirect (using grain beetles or fleas) life cycle. These cestodes are rarely found in laboratory rats and cause little pathogenesis unless in severe infections. An infection with R. nana may be diagnosed by observing the eggs in a fecal flotation or smear. Adult cestodes can also be seen on direct exam of the small intestine or the cysticercoid may be seen in histopathology of the small intestine. Treatment of affected animals is not recommended due to the zoonotic hazard.
8. Salmonellosis
In the rat, salmonellosis is usually attributed to Salmonella enteritidis or S. typhimurium. Clinical signs in rats are rare but may include lethargy, weight loss, conjunctivitis, poor hair coat, and soft stool or diarrhea, especially in sucklings or weanlings. Diagnosis is by culture of the feces. Differential diagnoses include Tyzzer’s disease, rotavirus, enterococcal enteropathy, cryptosporidiosis, or husbandry-related problems with feed, water, or bedding contamination. Since wild rodents are often Salmonella carriers, pest control is recommended as a means of prevention. Treatment of affected animals is not recommended since a chronic carrier state may result.
VI. Acknowledgements:
The authors would like to acknowledge the valuable assistance of Ms. Laura Casey in the production of the illustrations.
VII. Recommended Reading for the Practitioner and References
Recommended Reading
Harkness JE, Wagner JE. The Biology and Medicine of Rabbits and Rodents. Baltimore, Maryland: Williams and Williams, 1995. - Available from amazon.com -
Hillyer EV, Quesenberry KE, eds. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. New York, New York: WB Saunders, 1997. - Available from amazon.com -
Merideth A, Redrobe S, eds. BSAVA Manual of Exotic Pets. Glouchester, England: British Small Animal Veterinary Association, 2002. - Available from amazon.com -
Recommended References for the Researcher
Krinke GG. The Laboratory Rat. In: G. Bullock and T. E. Bunton, eds. The Handbook of Experimental Animals. 1st ed. San Diego: Academic Press, 2000; 756. - Available from amazon.com -
Flecknell PA. Laboratory Animal Anesthesia: A practical introduction for research workers and technicians. 2nd ed. London: Academic Press, 1996. - Available from amazon.com -
Flecknell PA, Waterman-Pearson A. Pain Management in Animals. London: WB Saunders, 2000; 184. - Available from amazon.com -
Fox JG, Anderson LC, Lowe FM, et al., eds. Laboratory Animal Medicine. 2nd ed. New York: Academic Press, 2002. - Available from amazon.com -
National Research Council. Guide for the Care and use of Laboratory Animals. Washington, DC: National Academy Press, 1996. - Available from amazon.com -
Poole T, ed. The UFAW Handbook on the Care and Management of Laboratory Animals. 7th ed. Malden, Massachussets: Blackwell Science, Ltd., 1999; 313-330. - Available from amazon.com -
Sharp PE, La Regina MC. The Laboratory Rat. In: M.A. Suckow, ed. The Laboratory Animal Pocket Reference Series. Boca Raton: CRC Press, 1998; 214. - Available from amazon.com -
Waynforth HB, Flecknell PA. Experimental and Surgical Technique in the Rat. 2nd ed. London: Academic Press, 1992. - Available from amazon.com -
Get access to all handy features included in the IVIS website
- Get unlimited access to books, proceedings and journals.
- Get access to a global catalogue of meetings, on-site and online courses, webinars and educational videos.
- Bookmark your favorite articles in My Library for future reading.
- Save future meetings and courses in My Calendar and My e-Learning.
- Ask authors questions and read what others have to say.
1. Hedrich HJ. History, strains, and models In: GJ Krinkle, ed. The Laboratory Rat. 1st ed. Vol. 1. San Diego: Academic Press, 2000; 3-16. - Available from amazon.com -
About
How to reference this publication (Harvard system)?
Affiliation of the authors at the time of publication
1,2Charles River Laboratories, Inc., Wilmington, MA, USA.
1Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
Comments (0)
Ask the author
0 comments