Rabbit Oryctolagus cuniculus

1. RabbitOryctolagus cuniculus Biology and Uses in Research

2. TAXONOMY • Class Mammalia • Order Lagamorpha • Family Leporidae • Genus Oryctolagus • Species cuninulus Lagomorphs are distinguished from rodents by their incisor teeth.

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

4. General Information Known as the domestic rabbit Derived from European wild rabbit Used as pets, meat producers or research Oryctolaguscuniculusis the only genus of the European rabbit Hares (lepus) and Cottontails (Sylvilagus) are in a different genera Fertile cross-genera mating do occur but offspring are infertile

5. Breeds and Varieties • Over 40 different breeds/varieties recognized by the American Rabbit Breeder Assn • Only a few used in meat production and labs • Many bred just for show quality • Most have definite molting period

6. Breeds • Of the six genus in the Subfamily Leporinae, only the European rabbit, Oryctolagus cuniculus is commonly used in research, testing, or teaching. • Three of the most commonly used breeds are the New Zealand White, American Dutch, and Californian.

7. New Zealand White • Most commonly used • White • Most popular • Used for food and laboratory • Mature weight 10 lbs/4.5 kgs • Docile

8. American Dutch • The American Dutch rabbit, is less than half the size of the New Zealand White, reaching a mature weight of only two kilograms. • There are several color varieties of the American Dutch breed, but the most common is the black and white • Second most popular in research

9. California Rabbit • Primarily for food • White fur with dark brown tips on feet, ears, nose and tail • Pigmentation thermolabile • Mature weight 10 lbs/4.5 kg

10. Chinchilla rabbit • Mature weight 10 lbs/4.5 kgs • Steel grey

11. Flemish Giant Checkered giant Largest breed Weight – 13 lbs Not commonly used – too big Mature slowly

12. Angora Used for fur Fur is plucked every 3 months 2 – 2 1/2 inches

13. Netherland Dwarf Smallest Weight – 2-3 lbs

14. Lop Eared Medium size Weight – 5-6 lbs Lop ears

15. Hair growth patterns • The hair growth patterns of the rabbit are somewhat unusual. After the rabbit's hair has been clipped, it may not grow back uniformly. • Notice in this rabbit that some patches of hair are longer than others. This can make interpretation of some skin tests difficult.

16. Skeletal mass • Only about 7% of the body weight of a rabbit is skeletal structure. • Compare the bone density of a cat (on the top) with the rabbit of approximately the same weight (on the bottom). • This is a lateral view radiograph. • The muscle mass of a rabbit relative to bone structure makes it highly susceptible to lumbar fracture or dislocation.

17. Dental Formula 2x (2/1 I, 0/0 C, 3/3 P, 3/2 M) = 28 • Teeth grown and wear continuously

18. Vital signs Normal vital signs will vary with the age and breed of the rabbit, but for a healthy animal they should fall within these ranges: • heart rate 130 - 325 • respiratory rate 32 -60 • rectal temp 101.3° F – 104° F

19. Urine • A healthy rabbit will produce about 50-75 mL of urine per kilogram of body weight each day. It will normally be dark yellow to brown and will appear turbid. This turbidity is due to mineral precipitates. Rabbit urine is normally alkaline with a pH of over 8.2 • The urine forms scale (a thick mineral coating) on cages as it dries.

20. Feces • Healthy rabbits produce two types of feces. • The droppings seen in the pan under the cage are hard fecal pellets that contain mostly waste fiber. • The other type is a softer feces that is produced in the cecum, and is often called cecotrophs or night feces. This material is rich in vitamins and protein, and the rabbit may consume it directly from the anus

21. Ear • An important feature of rabbits is the prominent blood vessels in their ears. • Rabbit ears are NOT handles and must never be used for restraint!  • The central artery is used for collecting large quantities of blood. The marginal ear vein is used for giving IV injections or collecting smaller quantities of blood

22. Hematology • The blood volume of a rabbit is approximately 56 ml/kg body weight. • Generally, 10 - 15% of the total volume can be taken as frequently as every two weeks without endangering the rabbit.

23. Hematology The normal range for the red blood cell count is 4.5 - 7.0 x 103. The total white blood cell count and differential fall within the range expected of most other species of laboratory animals, as shown here: Total WBC 4.6 - 13 X 103 Lymphocytes 30 - 50% Neutrophils 30 - 50% Monocytes 0 - 3% Eosinophils 0 - 2% Basophils 0- 7% (Ref Kozma, et al.).

24. Neutrophil, eosinophil • The rabbit neutrophil, shown on the left, contains granules that stain red with eosin. • Because of this staining characteristic, rabbit neutrophils are sometimes called pseudoeosinophils, amphophils, or heterophils.

25. Let's look at a dissection of a rabbit to study the internal organs that are most commonly relevant to research uses • This is a sagittal section of the head showing the long oropharynx (red pin), large fleshy tongue, and the sagittal niches. It also shows the relationship of the esophagus (yellow pin), to the trachea (blue pin), epiglottis (below the red pin), and nasopharynx (white pin). All of these features combine to make passing an endotracheal tube difficult

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

27. Lungs • The lungs differ from each other in size and construction. The right lung is normally larger, and it has three distinct lobes, whereas the left has only two. • This image shows the bilobed left lung

28. Abdominal cavity • The abdominal cavity is proportionately large, reflecting the high roughage content of the diet. The liver lies above the stomach. • The gall bladder is buried deep in the liver, and cannot be seen on this image. • The cecum is very large, and has about ten times the capacity of the stomach...

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

30. Female reproductive organs • This image shows the female reproductive organs -- the ovaries, uterine horns, and vagina which has been cut open longitudinally. • The uterine horns are separated their entire length. Each horn empties into a separate cervix and then into the vagina.

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

32. Reproduction • The female rabbit is called a doe;  she is generally larger than the male.  Females have four pairs of mammary glands and often has a pronounced dewlap (roll of fur under her chin). • Male rabbits are called bucks.  Bucks have no mammary tissue and their inguinal canals are open.  Group housed bucks may fight.  • 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 29 - 35 days.  Parturition ( kindling) occurs in the early morning in a nest that the doe makes by plucking fur from her dewlap, abdomen and sides. 

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

34. Sexing • To determine sex by genitalia, gently press the skin back from the genital opening and stretch the perineum. • In the male, this procedure will cause the penis to be everted. • The vulva of the female has the appearance of a slit. This procedure is necessary when sexing young rabbits.

35. Use in research

36. 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.

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

38. List (cont.) • Infectious diseases studied in the rabbit include staphylococcal infection, bacterial endocarditis, and Reiter's polyarthritis syndrome. Hereditary studies include familial hypercholesterolemia, dwarfism, and glaucoma.

39. Syphilis • There are some diseases of man for which only the rabbit can serve as a model. One of these is syphilis. The rabbit is the only other mammal in which syphilis occurs naturally. The causative agent of human syphilis, Treponema pallidium, cannot be grown in vitro. • But we can put the human organism into rabbits and study its growth there. If and when a vaccine is developed for human syphilis, trials will undoubtedly be conducted using the rabbit first.

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

41. Analogous systems • Four other characteristics of rabbits make them desirable for specific research tasks. • First, by analogous systems, we mean that some of the rabbit's organ systems are very similar to systems in man. • The rabbit is often the model of choice to study immune responses for this reason.

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

43. Reasons Not to Use • Size • Expense • Variable response to anesthetic agents • Prone to cardiovascular failure • Prone to stress related diseases (ex-coccidiosis)

44. Reproduction study • A doe has two uteri, each of which opens into the vagina through a separate cervix. This unique reproductive anatomy allows for an experimental group and a control group within a single biologic host. • Rabbits are also useful for studies that require precise timing during gestation, as a doe ovulates about ten hours after mating, and gestation is well defined at 30-32 days.

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