II   The Laboratory Rabbit

Reading Assignment:  in-text links

Study Guide

Taxonomy:

Rabbits were considered to be rodents until 1912, but differences in dentition resulted in the establishment of a new order, Lagomorpha, for rabbits and the related hares and pikas.  The taxonomic classification of the laboratory rabbit is:

Kingdom Animalia
Phylum Chordata
Class Mammalia
Order Lagomorpha
Family Leporidae
Genus Oryctolagus
Species Oryctolagus cuniculus

Rabbits and hares are leporids--they have long hind legs adapted for running at high speed over open ground.  The eastern cottontail, Sylvalagus floridanus, is the wild rabbit of the eastern United States.  It also belongs to the Family Leporidae, but is in a different genus from the domestic rabbit. 

There are over 100 breeds of rabbits.  The most common breeds used in research are the New Zealand White and the Dutch.  There are a variety of strains used in the laboratory, including the Watanabe rabbit that has a genetic predisposition to elevated low density lipoprotein (LDL cholesterol). 

                                  
                Cottontail               New Zealand White          Dutch Belted

History of the Rabbit in Research:

Rabbits were discovered in Spain in approximately 100 BC.  They were transported throughout the Roman Empire as an easily portable food source.  Domestication of the rabbit probably occurred when French monks set up walled compounds during the 1500s. 

Rabbits have been used in research for hundreds of years.  In the early 1600s, rabbit eyes were studied and glaucoma was described.  In the 1880s, Louis Pasteur did much of his research and testing of rabies vaccine using rabbits.

The Role of the Rabbit  in Research:

The domestic rabbit has many roles to play in animal research.

The rabbit is frequently utilized in safety testing for ocular and dermal irritation.  The most famous (or infamous) test is the Draize test, developed by JH Draize in 1944.  This is a controversial test that uses an objective scoring system to estimate irritancy.  Alternatives to this procedure have been developed, and, where allowed by government regulations, have been used in place of rabbits.

Rabbit eyes have other roles in research.  The corneal transplant was perfected in the rabbit before being performed on humans.  New Zealand White rabbits are prone to an inherited glaucoma, similar to the condition that occurs in people.

An important use of rabbits is polyclonal antibody production.  Rabbits are injected with a specific antigen, antibodies are manufactured against the antibodies, rabbit serum is harvested and the antibody is extracted.

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Rabbit Statistics:

Criterion	NZ White	Dutch
Life Span	5 - 6+ years	5 - 10 years
Adult Size	4 - 6 kg	1.5 - 2.5 kg
Temperature	99.1 - 102.9° F
Pulse	130 - 325 bpm
Respirations	30 - 60 rpm
Estrous Cycle	Continuous seasonal
Gestation	30 - 33 days
Weaning Age	4 - 6+ weeks

The Anatomy and Physiology of Rabbits:

Rabbits have a very delicate skeletal system.  Their bones make up 7 - 8% of their body weight  (cats bones make up approximately 13% of their body weight).  If rabbits kick with their powerful hind legs, they may fracture their spine between the sixth and seventh lumbar vertebrae.  Rabbit feet are fully furred and lack foot pads.  

Back fracture      

Lagomorph teeth are different from rodent teeth--they have two pair of incisors.  The second pair, called peg teeth,  are directly behind the large incisors of the upper jaw.  All of the rabbit's teeth (incisors, premolars and molars) are open-rooted, and malocclusion can be a serious problem.  The oral cavity is very small and the teeth in the lower jaw are narrower than those of the upper jaw.  

                     
       Peg teeth                     Malocclusion               Trichobezoar

The digestive system of the rabbit is very sensitive and prone to problems.  Rabbits are monogastric hindgut fermenters.  They are nibblers and must keep high fiber food in their gastrointestinal tact to maintain proper motility.  The small intestine is a common site for trichobezoars to form.  The cecum is the largest organ in the abdominal cavity, and produces soft mucousy cecotrophs, rich in B vitamins and protein.  

Rabbits have large fragile ears.   Rabbit ears are NOT handles and must never be used for restraint! 

The rabbit's eyes are large and set high on their head, facing sideways, which gives them a very wide field of vision.  They are very light sensitive, as the rabbit is a crepuscular animal, most active at dawn and dusk in the wild.  The nictitating membrane is well-developed.

Rabbits are obligate nose breathers;  open-mouthed breathing indicates respiratory distress.  The thoracic cavity is relatively small.   The combination of small mouth and thorax and narrow larynx make endotracheal intubation for anesthesia difficult.  In addition, laryngospasms may occur, causing bradycardia (slow heart rate), increasing the rabbit's anesthetic risk.

Rabbit urine is thick and creamy due to excessive calcium carbonate crystals.  Its  color varies from yellow to reddish brown (associated with dietary porphyrins).  The urine forms scale (a thick mineral coating) on cages as it dries.

Rabbit Reproduction:

The female rabbit is called a doe;  she is generally larger than the male.  Females have four mammary glands and often has a pronounced dewlap (roll of fur under her chin).

Sexing rabbits can be challenging.  The anogenital distance is not significantly diferent.  It is necessary to express the genitalia.  If a doughnut-shaped structure emerges, you are looking at the penis of a male.  If a slit is visible, it is a female. 

            
        Male                     Female                        Dewlap

The rabbit is an induced ovulator and has no distinct estrous cycle, although she is typically a spring breeder.  The doe ovulates ten to twelve hours after mating.  When she is receptive to a male, she exhibits a posture called lordosis, elevating her hindquarters.

Gestation in rabbits is 30 - 33 days.  Parturition ( kindling) occurs in the early morning in a nest that the doe makes by plucking fur from her dewlap, abdomen and sides.  The doe nurses her kits for approximately five minutes once or twice a day.  A rabbit's litter usually consists of 4 - 5 kits (for small rabbit breeds) to 8 - 12 kits (for the larger breeds).  Rabbit kits are altricial.  The kits stay in the nest for three weeks, growing hair at five days, opening their ears at eight days, and the eyes open around ten days of age.  The kits are weaned when they are four to six weeks old.

                    
  Newborn kits                  8 days old                     28 days old

Pseudopregnancy  may occur, especially if females are housed together.  The does may gain weight, produce milk and exhibit nesting behavior, but are not truly pregnant.  If a doe is disturbed soon after her kits are born, she may cannibalize them.

Male rabbits are called bucks.  Bucks have no mammary tissue and their inguinal canals are open.  Group housed bucks may fight. 

A monogamous mating system is most frequently used when breeding rabbits.  The doe should be brought to the buck's cage, because she may attack him as an intruder in her own territory (cage).  

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Rabbit Temperament:

Rabbits are timid animals, generally calm, and they rarely make noise.  They are sensitive to loud noises, however, and may thump their hind feet or scream when frightened or excited. Some rabbits are more aggressive, and may charge or bite people.

Rabbit Technical Procedures:

Because of their timid personality and fragile skeleton, rabbits must be restrained carefully and securely.  

                                      
   Bad holds (no support of hindquarters)                                 Good hold

Blood collection can be accomplished by using the auricular artery or marginal vein on the pinna, by cardiac puncture (terminal procedure) or by jugular or saphenous venipuncture.  

USDA requires all survival surgery in nonrodent species, including the rabbit, to be performed in a dedicated surgery area with strict aseptic conditions.

Rabbit Husbandry:

Wild rabbits are crepuscular animals, but domestic rabbits readily adapt to a diurnal laboratory pattern.  

Rabbits are usually housed individually to avoid fights or pseudopregnancies.  Group-housed rabbits, however, have greater social interaction and enrichment.  If it is not precluded by the experimental protocol or the temperament of the rabbits, group housing should be used.  In the laboratory, rabbit cages  are generally stainless steel suspended cages, with a solid lower half to prevent urine spraying and bars on the top half for ventilation.  The cage should be tall enough for the rabbit to stand on its hind legs.  

                 
   Cage bank                      Cage detail            Indirect bedding

The flooring is metal mesh or slats (indirect bedding) so that urine and feces f all through to a collection tray underneath.  Due to the high mineral content of the urine, an acid cleaner must be used to remove scale that accumulates on the floor of the cage.

The temperature in the rabbit's room and cage temperatures should be 60-70° F.  Rabbits are very heat sensitive and lack sweat glands.  Excessive heat may cause rabbits to stop drinking, which can lead to anorexia, dehydration, starvation and death.  Optimal humidity is 40 - 60%.

Like other laboratory animals, rabbits are fed complete commercial pellets.  The pellets are high fiber  to prevent gastrointestinal problems and should be available on a constant basis--rabbits are nibblers and must eat constantly.  Supplemental grass hay is recommended to encourage digestion and decrease trichobezoars and diarrhea.  Gastrointestinal blockages from ingested hair  and other foreign bodies and the rabbit's inability to vomit make obstruction a common  digestive disorder.  Elevated J-feeders are the most common method to provide food.   These feeders prevent fecal contamination of the food; it is important, however, to ensure that the food doesn't cake within the feeder and that it fills the eating area.

                
     Pellets                   Loose hay             Timothy hay cubes     J-shaped feeder

Rabbits drink a considerable amount of water and may stop eating if water is not available.

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Rabbit Health and Disease:

Many rabbit colonies are storehouses of disease; rabbits are rarely completely healthy.  Rabbits are susceptible to a variety of viral and bacterial pathogens.  Because rabbits are very sensitive and timid, they are frequently stressed, making disease more likely.  Rabbits may be infected with many different parasites and fungi.  They may inherit a predisposition to diseases such as malocclusion.  Poor husbandry may lead to gastrointestinal problems and foot ulcers.  

Infectious-

The most common infectious disease of the laboratory rabbit is pasteurellosis ("snuffles"), caused by the bacterium Pasteurella multicida.  It is transmitted by direct contact between infected rabbits, by fomites and by vertical transmission from the doe to her kits at birth.  Pasteurella infection is often subclinical, and may only develop into pasteurellosis if the rabbits are stressed by experimental procedures or deficient husbandry.  Sick rabbits typically have a yellow mucopurulent ocular and nasal discharge, and their  face and paws may be discolored from grooming.  Sneezing, audible respirations, râles and rattles may be heard.  Pneumonia,  otitis media (leading to torticolis) and abscesses may occur.  Some rabbits die suddenly with few other signs.  Pasteurellosis is diagnosed by clinical signs, microbiological culture and blood testing.  Treatment is usually symptomatic; Pasteurella cannot be eradicated from an infected animal, but antibiotics such as Baytril® may be helpful.  Sick animals should be culled and a new colony established using Pasteurella- free stock.  Infected breeding stock should be culled or spayed or castrated.  Bordetella bronchiseptica infection may occur concurrently with Pasteurella.  It generally causes little problem in rabbits, but is deadly to guinea pigs and care must be taken to avoid exposing them.

With their delicate digestive tract, rabbits are susceptible to bacteria-induced diarrhea.  Enterotoxemia causes scours (diarrhea) due to Clostridium perfringens.  It is spread by the fecal-oral route and is characterized by acute onset watery greenish-brown diarrhea, fetid odor, increased intestinal sounds, lethargy, anorexia and depression.  Clostridial infections are diagnosed by clinical signs and bacterial culture.  Treatment is supportive, including increased fiber and yogurt (to supply "good" bacteria), and prevention is preferred.

Rabbits are also susceptible to Clostridium piliformes, causing Tyzzer's disease, Treponema cuniculi, the cause of venereal spirochetosis (rabbit syphilis), and Francisella tularensis, a zoonotic bacterium that causes tularemia.

Noninfectious-

Malocclusion is a problem in rabbits (their teeth are all open-rooted).  It is a genetic trait, and rabbits with malocclusion should not be bred.  Signs may include ptyalism (excessive drooling), anorexia and death from starvation.

Trichobezoars may develop from excess groomed fur trapped in gastrointestinal tract. Hair is always present in the stomach and intestines of rabbits, so there is controversy over the significance of this hair.  Signs of animals with impaction due to trichobezoars may cause diarrhea, constipation and weight loss.  Treatment is generally supportive and may include digestive aids (such as Laxatone® or papaya) or surgery.  

Sensitivity to oral antibiotics may lead to severe diarrhea and oral penicillin-type antibiotics must not be used.

Ulcerative pododermatitis  (sore hocks) may develop due to improper flooring.  Some rabbits may require a solid section to their floor.  

Moist dermatitis (also called slobbers, wet dewlap or urine scald) is a pus-producing rash of the skin.  It is due to variety of traumatic and infectious agents, often secondary to continually wet skin. This wet skin may occur due to malocclusion (ptyalism), rhinitis and conjunctivitis associated with an upper respiratory infection, chronic diarrhea, urinary incontinence or open water bowls.  Bacteria such as Staphylococcus, Streptococcus, and Pseudomonas may be present.  A rabbit with moist dermatitis can be recognized by the rash; deep ulcers may develop on the inflamed area.  The best treatment is to prevent it from happening, because it is generally associated with inadequate husbandry.  Teeth should be trimmed, diarrhea and respiratory infections should be treated, and bedding should be cleaned as needed.  Lesions should be clipped, cleaned and treated with topical antibiotics.

Does are susceptible to uterine adenocarcinomas, the most common neoplasm of rabbits.

Splay leg is a developmental musculoskeletal condition seen in rabbits that are only a few days to a few months old.  It is recognized by the rabbit's inability to adduct one to all of its limbs.  It is a genetic condition and there is no treatment.

Parasites-

Psoroptes cuniculi is the rabbit ear mite.  It is transmitted by direct contact.  Signs include  inflammation and dry brown crusts on the inner pinna.  Affected rabbits scratch and shake their heads.  P cuniculi is treated with ivermectin.  DO NOT  remove the crusts--they are very painful.

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