RabbitRabbit Oryctolagus cuniculusOryctolagus cuniculus

Biology and Uses in Research Biology and Uses in Research

TAXONOMYTAXONOMY

ClassClass MammaliaMammalia OrderOrder LagamorphaLagamorpha FamilyFamily LeporidaeLeporidae GenusGenus OryctolagusOryctolagus SpeciesSpecies cuninuluscuninulus

Lagomorphs are distinguished from Lagomorphs are distinguished from rodents by their incisor teeth.rodents by their incisor teeth.

Teeth Teeth

Lagomorphs Lagomorphs have have six incisor teeth,six incisor teeth, including the small including the small teeth (frequently teeth (frequently called peg teeth) called peg teeth) directly behind the directly behind the large upper large upper incisors. By incisors. By contrast, rodents contrast, rodents have only four have only four incisors.incisors.

General InformationGeneral Information

Known as the domestic rabbitKnown as the domestic rabbit

Derived from European wild rabbitDerived from European wild rabbit

Used as pets, meat producers or researchUsed as pets, meat producers or research

Oryctolagus cuniculusOryctolagus cuniculus is the only genus of is the only genus of the European rabbitthe European rabbit

Hares (lepus) and Cottontails (Sylvilagus) Hares (lepus) and Cottontails (Sylvilagus) are in a different generaare in a different genera

Fertile cross-genera mating do occur but Fertile cross-genera mating do occur but offspring are infertileoffspring are infertile

Breeds and VarietiesBreeds and Varieties

Over 40 different breeds/varieties Over 40 different breeds/varieties recognized by the American Rabbit recognized by the American Rabbit Breeder AssnBreeder Assn

Only a few used in meat production Only a few used in meat production and labsand labs

Many bred just for show qualityMany bred just for show quality Most have definite molting periodMost have definite molting period

Breeds Breeds

Of the six genus in the Subfamily Of the six genus in the Subfamily Leporinae, only the European rabbit, Leporinae, only the European rabbit, Oryctolagus cuniculusOryctolagus cuniculus is commonly is commonly used in research, testing, or used in research, testing, or teaching. teaching.

Three of the most commonly used Three of the most commonly used breeds are the breeds are the New Zealand White, New Zealand White, American Dutch, and CalifornianAmerican Dutch, and Californian..

New Zealand WhiteNew Zealand White

Most commonly Most commonly usedused

WhiteWhite Most popularMost popular Used for food and Used for food and

laboratorylaboratory Mature weight 10 Mature weight 10

lbs/4.5 kgslbs/4.5 kgs DocileDocile

American DutchAmerican Dutch The American Dutch The American Dutch

rabbit, is less than half rabbit, is less than half the size of the New the size of the New Zealand White, Zealand White, reaching a mature reaching a mature weight of only weight of only two two kilogramskilograms. .

There are several There are several color varieties of the color varieties of the American Dutch American Dutch breed, but the most breed, but the most common common is the black is the black and white and white

Second most popular Second most popular in researchin research

California RabbitCalifornia Rabbit

Primarily for Primarily for foodfood

White fur with White fur with dark brown tips dark brown tips on feet, ears, on feet, ears, nose and tailnose and tail

Pigmentation Pigmentation thermolabilethermolabile

Mature weight Mature weight 10 lbs/4.5 kg10 lbs/4.5 kg

Chinchilla rabbitChinchilla rabbit

Mature weight Mature weight 10 lbs/4.5 kgs10 lbs/4.5 kgs Steel greySteel grey

Flemish GiantFlemish Giant

Checkered giantCheckered giant

Largest breedLargest breed

Weight – 13 lbsWeight – 13 lbs

Not commonly used – too bigNot commonly used – too big

Mature slowlyMature slowly

AngoraAngora

Used for furUsed for fur

Fur is Fur is plucked plucked every 3 monthsevery 3 months

2 – 2 1/2 inches2 – 2 1/2 inches

Netherland DwarfNetherland Dwarf

SmallestSmallest

Weight – 2-3 lbsWeight – 2-3 lbs

Lop EaredLop Eared

Medium sizeMedium size

Weight – 5-6 lbsWeight – 5-6 lbs

Lop earsLop ears

Hair growth patternsHair growth patterns

The hair growth patterns The hair growth patterns of the rabbit are of the rabbit are somewhat unusual. somewhat unusual. After the rabbit's hair has After the rabbit's hair has been clipped, it may not been clipped, it may not grow back uniformly. grow back uniformly.

Notice in this rabbit that Notice in this rabbit that some patches of hair are some patches of hair are longer than others. This longer than others. This can make interpretation can make interpretation of some skin tests of some skin tests difficult.difficult.

Skeletal massSkeletal mass

Only about Only about 7% of the body 7% of the body weight of a rabbit is weight of a rabbit is skeletal structure. skeletal structure.

Compare the bone density Compare the bone density of a cat (on the top) with of a cat (on the top) with the rabbit of approximately the rabbit of approximately the same weight (on the the same weight (on the bottom). bottom).

This is a lateral view This is a lateral view radiograph. radiograph.

The muscle mass of a The muscle mass of a rabbit relative to bone rabbit relative to bone structure makes it highly structure makes it highly susceptible to lumbar susceptible to lumbar fracture or dislocation. fracture or dislocation.

Dental Formula Dental Formula

2x (2/1 I, 0/0 C, 3/3 P, 3/2 M) = 282x (2/1 I, 0/0 C, 3/3 P, 3/2 M) = 28 Teeth grown and wear continuouslyTeeth grown and wear continuously

Vital signsVital signs

Normal vital signs will vary with the Normal vital signs will vary with the age and breed of the rabbit, but for age and breed of the rabbit, but for a healthy animal they should fall a healthy animal they should fall within these ranges:within these ranges:

heart rate 130 - 325heart rate 130 - 325 respiratory rate 32 -60respiratory rate 32 -60 rectal temp 101.3rectal temp 101.3°° F – 104 F – 104°° F F

Urine Urine A healthy rabbit will produce about A healthy rabbit will produce about 50-75 mL of 50-75 mL of

urine per kilogram of body weight each dayurine per kilogram of body weight each day. It . It will normally be dark yellow to brown and will will normally be dark yellow to brown and will appear turbid. This turbidity is due to mineral appear turbid. This turbidity is due to mineral precipitates. Rabbit urine is normally alkaline precipitates. Rabbit urine is normally alkaline with a with a pH of over 8.2pH of over 8.2

The urine forms scale (a thick mineral coating) The urine forms scale (a thick mineral coating) on cages as it dries. on cages as it dries.

FecesFeces Healthy rabbits Healthy rabbits

produce produce two types of two types of fecesfeces. .

The droppings seen in The droppings seen in the pan under the cage the pan under the cage are hard fecal are hard fecal pellets pellets that contain mostly that contain mostly waste fiber. waste fiber.

The other type is a The other type is a softer feces that is softer feces that is produced in the cecum, produced in the cecum, and is often called and is often called cecotrophs or night cecotrophs or night feces. This material is feces. This material is rich in vitamins and rich in vitamins and protein, and the rabbit protein, and the rabbit may consume it may consume it directly from the anusdirectly from the anus

EarEar

An important feature of An important feature of rabbits is the rabbits is the prominent blood prominent blood vessels in their ears. vessels in their ears.

Rabbit ears are NOT Rabbit ears are NOT handles and must handles and must never be used for never be used for restraint!  restraint! 

The central artery is The central artery is used for collecting used for collecting large quantities of large quantities of bloodblood. The marginal . The marginal ear vein is used for ear vein is used for giving IV injections or giving IV injections or collecting smaller collecting smaller quantities of blood quantities of blood

Hematology Hematology

The blood volume of a rabbit is The blood volume of a rabbit is approximately approximately 56 ml/kg body weight56 ml/kg body weight. .

Generally, 10 - 15% of the total Generally, 10 - 15% of the total volumevolume can be taken as frequently as can be taken as frequently as every two weeks without every two weeks without endangering the rabbit.endangering the rabbit.

HematologyHematology

The normal range for the red blood cell The normal range for the red blood cell count is count is 4.5 - 7.0 x 103.4.5 - 7.0 x 103. The total white The total white blood cell count and differential fall within blood cell count and differential fall within the range expected of most other species of the range expected of most other species of laboratory animals, as shown here:laboratory animals, as shown here:

Total WBC 4.6 - 13 X 103Total WBC 4.6 - 13 X 103Lymphocytes 30 - 50%Lymphocytes 30 - 50%Neutrophils 30 - 50%Neutrophils 30 - 50%Monocytes 0 - 3%Monocytes 0 - 3%Eosinophils 0 - 2%Eosinophils 0 - 2%Basophils 0- 7% (Ref Kozma, et Basophils 0- 7% (Ref Kozma, et

al.).al.).

Neutrophil, eosinophilNeutrophil, eosinophil

The rabbit neutrophil, The rabbit neutrophil, shown on the left, shown on the left, contains granules that contains granules that stain red with eosin. stain red with eosin.

Because of this Because of this staining staining characteristic, rabbit characteristic, rabbit neutrophils are neutrophils are sometimes called sometimes called pseudoeosinophils, pseudoeosinophils, amphophils, or amphophils, or heterophils. heterophils.

Let's look at a dissection of a rabbit to study the Let's look at a dissection of a rabbit to study the internal organs that are most commonly relevant to internal organs that are most commonly relevant to

research usesresearch uses

This is a sagittal section This is a sagittal section of the head showing the of the head showing the long oropharynx (red long oropharynx (red pin), large fleshy tongue, pin), large fleshy tongue, and the sagittal niches. and the sagittal niches. It also shows the It also shows the relationship of the relationship of the esophagus (yellow pin), esophagus (yellow pin), to the trachea (blue pin), to the trachea (blue pin), epiglottis (below the red epiglottis (below the red pin), and nasopharynx pin), and nasopharynx (white pin). All of these (white pin). All of these features combine to features combine to make passing an make passing an endotracheal tube endotracheal tube difficult difficult

Thoracic cavityThoracic cavity

Dissection into the Dissection into the thoracic cavity, thoracic cavity, shows the heart, shows the heart, which is relatively which is relatively small for the size of small for the size of the animalthe animal -- about -- about 1/2 that of a cat of 1/2 that of a cat of the same size. This the same size. This becomes important becomes important when attempting to when attempting to collect blood via collect blood via cardiac puncture. cardiac puncture.

LungsLungs

The lungs The lungs differ differ from each other in from each other in size and size and construction.construction. The The right lung is right lung is normally larger,normally larger, and and it has three distinct it has three distinct lobes, whereas the lobes, whereas the left has only two. left has only two.

This image shows This image shows the bilobed left lung the bilobed left lung

Abdominal cavityAbdominal cavity

The abdominal cavity The abdominal cavity is proportionately is proportionately large, reflecting the large, reflecting the high roughage high roughage content of the diet. content of the diet. The liver lies above The liver lies above the stomach. the stomach.

The gall bladder is The gall bladder is buried deep in the buried deep in the liver, and cannot be liver, and cannot be seen on this image. seen on this image.

The cecum is very The cecum is very large, and has about large, and has about ten times the ten times the capacity of the capacity of the stomachstomach... ...

StomachStomach

...which is large, ...which is large, thin-walled, not thin-walled, not compartmentalized, compartmentalized, and relatively and relatively aglandular. aglandular. The pH The pH in an adult rabbit in an adult rabbit stomach is very acidstomach is very acid

Female reproductive organsFemale reproductive organs

This image shows the This image shows the female reproductive female reproductive organs -- the ovaries, organs -- the ovaries, uterine horns, and uterine horns, and vagina which has vagina which has been cut open been cut open longitudinally. longitudinally.

The uterine horns are The uterine horns are separated their entire separated their entire length. Each horn length. Each horn empties into a empties into a separate cervix and separate cervix and then into the vagina. then into the vagina.

PlacentaPlacenta

The placental barrier in the rabbit is The placental barrier in the rabbit is hemochorialhemochorial, which means that the , which means that the membrane enclosing the fetus is in membrane enclosing the fetus is in direct contact with maternal blood. direct contact with maternal blood. This means it is similar to the human This means it is similar to the human barrier, making the rabbit a good barrier, making the rabbit a good model for studying transmission of model for studying transmission of agents through the placenta. agents through the placenta.

Reproduction Reproduction The female rabbit is called a doe;  she is The female rabbit is called a doe;  she is

generally larger than the male.  Females have generally larger than the male.  Females have four pairs of mammary glands and often has a four pairs of mammary glands and often has a pronounced dewlap (roll of fur under her chin). pronounced dewlap (roll of fur under her chin).

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

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

Gestation in rabbits is 29 - 35 daysGestation in rabbits is 29 - 35 days.  .  Parturition Parturition ( kindling) ( kindling) occurs in the early morning in a nest occurs in the early morning in a nest

that the doe makes by plucking fur from her that the doe makes by plucking fur from her dewlap, abdomen and sides.  dewlap, abdomen and sides. 

Sexing Sexing Differentiating mature males from females is Differentiating mature males from females is

fairly easy. As females mature, they develop a fairly easy. As females mature, they develop a soft soft fold of skin below their chin, from which they fold of skin below their chin, from which they pluck hair when nesting. This is called a dewlappluck hair when nesting. This is called a dewlap. . Compare the profile of the female, left, with the Compare the profile of the female, left, with the male at the right.male at the right.

SexingSexing

To determine sex by To determine sex by genitalia, genitalia, gently press gently press the skin back from the the skin back from the genital opening and genital opening and stretch the perineumstretch the perineum. .

In the male, this In the male, this procedure will cause procedure will cause the penis to be the penis to be everted. everted.

The vulva of the female The vulva of the female has the appearance of has the appearance of a slit. This procedure a slit. This procedure is necessary when is necessary when sexing young rabbits. sexing young rabbits.

Use in research Use in research

History of the Rabbit in History of the Rabbit in Research:Research:

Rabbits were discovered in Spain in Rabbits were discovered in Spain in approximately 100 BC.  They were transported approximately 100 BC.  They were transported throughout the Roman Empire as an easily throughout the Roman Empire as an easily portable food source.  portable food source. 

Domestication of the rabbit probably occurred Domestication of the rabbit probably occurred when French monks set up walled compounds when French monks set up walled compounds during the 1500s.  during the 1500s. 

Rabbits have been used in research for hundreds Rabbits have been used in research for hundreds of years.  of years.  In the early 1600s, rabbit eyes were In the early 1600s, rabbit eyes were studied and glaucoma was describedstudied and glaucoma was described.  . 

In the 1880s, Louis Pasteur did much of his In the 1880s, Louis Pasteur did much of his research and testing of research and testing of rabies vaccine using rabies vaccine using rabbitsrabbits..

List of historical usesList of historical uses

The cause and treatment of many human The cause and treatment of many human diseases have been studied using the rabbit diseases have been studied using the rabbit as a model. Because of its response to as a model. Because of its response to different diets, the rabbit was the first different diets, the rabbit was the first animal model used to study animal model used to study atherosclerosis.atherosclerosis. Other noninfectious diseases studied in the Other noninfectious diseases studied in the rabbit include rabbit include osteoarthritis, pregnancy osteoarthritis, pregnancy toxemia, endometrial adenocarcinoma, drug toxemia, endometrial adenocarcinoma, drug teratogenesis, hydrocephalus, muscular teratogenesis, hydrocephalus, muscular dystrophy, glomerulonephritis, and dystrophy, glomerulonephritis, and gallstonesgallstones. .

List (cont.)List (cont.)

Infectious diseases studied in the Infectious diseases studied in the rabbit include staphylococcal rabbit include staphylococcal infection, bacterial infection, bacterial endocarditis, and endocarditis, and Reiter's polyarthritis syndromeReiter's polyarthritis syndrome. . Hereditary studies include familial Hereditary studies include familial hypercholesterolemia, dwarfism, hypercholesterolemia, dwarfism, and glaucoma. and glaucoma.

Syphilis Syphilis

There are some diseases of There are some diseases of man for which only the man for which only the rabbit can serve as a model. rabbit can serve as a model. One of these is syphilis.One of these is syphilis. The The rabbit is the only other rabbit is the only other mammal in mammal in which syphilis which syphilis occurs naturallyoccurs naturally. The . The causative agent of human causative agent of human syphilis, syphilis, Treponema Treponema pallidiumpallidium, cannot be grown , cannot be grown in vitro.in vitro.

But we can put the human But we can put the human organism into rabbits and organism into rabbits and study its growth there. If and study its growth there. If and when a vaccine is developed when a vaccine is developed for human syphilis, trials will for human syphilis, trials will undoubtedly be conducted undoubtedly be conducted using the rabbit first. using the rabbit first.

Pet vaccinationPet vaccination

Animals have also Animals have also benefited from benefited from research using rabbits. research using rabbits. Pasteur developed a Pasteur developed a vaccine to protect vaccine to protect dogs from rabies by dogs from rabies by using dried spinal cord using dried spinal cord from rabbits that had from rabbits that had been experimentally been experimentally infected infected

Analogous systemsAnalogous systems

Four other characteristics of rabbits Four other characteristics of rabbits make them desirable for specific make them desirable for specific research tasks. research tasks.

First, by analogous systems, we mean First, by analogous systems, we mean that some of the rabbit's organ systems that some of the rabbit's organ systems are very similar to systems in man. are very similar to systems in man.

The rabbit is often the model of choice The rabbit is often the model of choice to study immune responses for this to study immune responses for this reason. reason.

Size Size

Rabbits may be Rabbits may be preferred over other preferred over other common laboratory common laboratory animals because of animals because of their size. They have their size. They have sufficient blood volume sufficient blood volume to allow for large blood to allow for large blood samples to be taken samples to be taken either singly or serially. either singly or serially. Because of their size, Because of their size, they may be preferred they may be preferred over rodents for studies over rodents for studies that require that require temperature monitoring temperature monitoring or surgical procedures.or surgical procedures.

Reasons Not to UseReasons Not to Use

SizeSize ExpenseExpense Variable response to anesthetic Variable response to anesthetic

agentsagents Prone to cardiovascular failureProne to cardiovascular failure Prone to stress related diseases (ex-Prone to stress related diseases (ex-

coccidiosis)coccidiosis)

Reproduction study Reproduction study A doe has two uteri, A doe has two uteri,

each of which opens each of which opens into the vagina through into the vagina through a separate cervix. This a separate cervix. This unique reproductive unique reproductive anatomy allows for an anatomy allows for an experimental group and experimental group and a control group within a a control group within a single biologic host. single biologic host.

Rabbits are also useful Rabbits are also useful for studies that require for studies that require precise timing during precise timing during gestation, as a doe gestation, as a doe ovulates about ten ovulates about ten hours after mating, and hours after mating, and gestation is well defined gestation is well defined at 30-32 days. at 30-32 days.

Susceptibility to diseaseSusceptibility to disease

The last of these characteristics that The last of these characteristics that make the rabbit valuable for make the rabbit valuable for specialized studies is its specialized studies is its susceptibility to spontaneous and susceptibility to spontaneous and induced diseases; such as syphilis, induced diseases; such as syphilis, herpetic conjunctivitis, tumors herpetic conjunctivitis, tumors associated with papilloma viruses, associated with papilloma viruses, glaucoma, hyperlipidemia, and glaucoma, hyperlipidemia, and nutritional muscular dystrophy. nutritional muscular dystrophy.