The Cat in Biomedical Research

Research Animal Methods
VSC 543/443 -  Fall 2011
Lecture Notes for 10/10/2011
Original content by: Michael S. Rand, DVM

Paula D. Johnson, DVM
Assistant Veterinary Specialist- University Animal Care
University of Arizona - Tucson, AZ


  1.  INTRODUCTION

The cat, like the dog, was one of the first domestic animals that scientists observed.  Early studies involved the falling reflex and integration of the mechanisms of balance.  Researchers commonly used the cat in psychological, socialization, and learning studies.  The occurrence of blood cancers and solid tumors such as lymphomas, leukemia, and adenocarcinoma and endocrine tumors comparable to those of humans makes the cat valuable to cancer research. Cats are useful models for studies into the AIDS virus, and as models for research involving the brain, genetics, head-eye-ears, pharmacology, nutrition, virology, and surgical technique development.  While cats provide an important and necessary animal model, they only comprise less than 1% of the total animals used in research, and this number has dropped dramatically over the years.

Cats and humans have several similar infectious diseases: hemolytic anemia of the cat is similar to Oroya fever of man; toxoplasmosis occurs among both species; Chlamydia, cholera, sporotrichosis, and filariasis infect both cats and humans. Cats are, therefore, noteworthy models for the development of effective treatments and preventative measures of infectious diseases. Selective models in which cats are currently used are given in sections VII through XV.

There are also many benefits to animal diseases/disorders/and preventive measures that have occurred as a result of using the cat as a model in biomedical research. This includes improved animal surgical procedures and new vaccines to prevent animal diseases. As stated by the Foundation for Biomedical Research, “Thanks to research, the life expectancy of house cats has been expanded more than eight years. In fact, some pets can live up to more than 20 years.”

Sources of Cats

Purpose bred:   These cats are raised specifically for research.  The advantages include more uniform genetic control; often from a specific breed or from a specific foundation stock.  Specific conditions can be reproduced, and a pedigree may be available.  There are fewer health problems, animals have excellent vaccination histories, and are free of common diseases and parasites.  They are also accustomed to cage life.  The disadvantages would be most significantly the cost, but also the lack of socialization (producing rather shy animals). Random-Source:  These are cats which are not specifically bred for research and are purchased form pounds, Class B dealers, or donated to research.  They may be unconditioned, not quarantined or acclimated, or conditioned.   The conditioned animals have been quarantined and acclimated to produce a stable, disease free animal.  This process can take as long as 30 to 60 days and the animals are less likely to have respiratory disease, parasites, etc.  The disadvantage is the cost increase the longer the cats are in the program.
  1. CRITERIA FOR SELECTING EXPERIMENTAL ANIMALS

Scientists who are planning experiments evaluate both animal and non-animal approaches.  If there are no suitable alternatives to the use of live animals, the appropriate species is selected on the basis of various scientific and practical factors, including the following:

  • Which species will yield the most scientifically accurate and interpretable results?
  • According to critical review of the scientific literature, which species have provided the best, most applicable historical data?
  • On which species will data from the proposed experiments be most relevant and useful to present and future investigators?
  • Which species have special biologic or behavioral characteristics that make them most suitable for the planned studies?
  • Which species have features that render them inappropriate for the planned studies?
  • Which species present the fewest or least severe biologic hazards to the research team?
  • Which species require the fewest number of animals?
  • Which species that meet the above criteria are most economical to acquire and house?

For some scientific experiments, the answer to those questions will be the domestic cat.  The size, biologic features, and cooperative, docile nature of the well-socialized cat make it the model of choice for a variety of scientific inquiries.  The contributions of the cat to human health and well-being are numerous.

Although research with cats is often primarily to benefit humans, it has also greatly benefited cats that are kept as companion animals.  Examples of the benefits to cats are improvements in diagnostic techniques; treatments for diabetes and arthritis; surgical procedures for correcting or treating cardiovascular, orthopedic, and neurologic disorders; and therapies for bacterial, neoplastic, and autoimmune diseases. Moreover, cats have been necessary for the development of vaccines that protect companion animals against viral diseases (e.g. feline panleukopenia, feline viral rhinotracheitis, feline calicivirus, and feline leukemia) and drugs that prevent parasitic diseases.

Genetic, biological, and behavioral factors are also important factors to consider when determining the model of choice.  There are numerous references available that discuss these factors at length.

Hazards
Unvaccinated cats may harbor rabies virus, and pre-exposure immunization should be made available to personnel who are at substantial risk of infection.  Cats also have internal and external parasites that can be shared with humans.  Table 2 lists selected zoonoses.  Personnel can develop allergies to feline dander and saliva, and can be bitten or scratched.  To deal with these and other animal-related health problems, institutions must provide occupational health programs for personnel who work in animal facilities or have substantial animal contact.

Cat-Scratch Disease  (Bartonella henselae Infection)
Cat-scratch disease (CSD) is a bacterial disease that results from a cat or kitten scratch, bite, and while fleas have been infected, it is unclear if they can transmit CSD to humans). Kittens are more likely to be infected and about 40% of cats carry B. henselae at some time in their lives.  A cat does not need to be sick, or show signs of infection, to carry the bacteria associated with cat-scratch disease.  Signs and symptoms usually manifest in one to two weeks after the incident. The symptoms include:  a pus-filled sore at the site of injury (mild to severe); swollen and tender lymph nodes (especially around the head, neck, and upper limbs); fever; headache; fatigue; and poor appetite.  There are usually no long-term complications, and symptoms may disappear without treatment, although it is always recommended to consult a physician, as antibiotics may be needed, and severe complications, while rare, may occur. Individuals that are immunocompromised are at a higher risk, thus should take extra care.  Avoiding activity that can lead to cat/kitten scratches and bites is the best method of prevention.  Thoroughly cleaning any bite or scratch immediately with running water and soap is very important to decreasing the probability of infection and complications.  Other methods to prevent infection include:  not allowing cats to lick open wounds on a human; control fleas; if an infection develops (with pus and pronounced swelling) where you were scratched or bitten by a cat or develop symptoms, including fever, headache, swollen lymph nodes, and fatigue, contact your physician.

Rabies
Rabies is caused by a virus that enters the body through a wound, usually from a bite of an infected animal, and eventually affects the brain.  Animals that can carry rabies include: Cat, Dog, Ferret, Raccoons. Bats, Cattle, Rabbits, Skunks, Foxes. If an animal is suspected of rabies, it must be quarantined for ten days or euthanized and the brain submitted for testing. Animals infected with rabies exhibit unusual behavior, cats that are usually shy, could suddenly become aggressive; dogs which are usually friendly, may suddenly become shy. Signs may include: drooling or foaming at the mouth, the appearance of being injured or are having trouble walking.

If an animal is suspected of rabies it must be quarantined, or the brain submitted for testing – State laws will determine the regulations and guidelines that must be followed.

If a person is bitten, immediately seek emergency medical care. A preventive vaccine may be administered to prevent the disease. Once symptoms develop, however, it may be too late to treat the disease. Early signs and symptoms of rabies in people include:  restlessness, fatigue, loss of appetite, headache, fever, itching at the site of the animal bite.  As the virus replicates, the disease progresses and infected people can become aggressive and alternate between periods of wild excitement and seemingly normal behavior, eventually becoming unconscious and paralyzed. Rabies is nearly always fatal.

Because of the seriousness of the disease, all cats in research must be vaccinated for rabies. This is also a good reminder to have pets vaccinated and the reason it is recommended to not leave your pets loose outside unsupervised where they can encounter other animals that may carry rabies.
  1. HOUSING

The criteria for housing are specifically given in the Guide for the Care and Use of Laboratory Animals.  The design and management of feline facilities are discussed in this reference and may also be found in  “Laboratory Animal Management – Cats”  ILAE, 1978d, and  in “Laboratory Animal Housing”  ILAR, 1978c.

Primary enclosures are one of the most important factors in the environment of the research cat.  The physical comfort of the animal is a primary consideration when evaluating a caging system.  It influences the well being of the animals well as the biological responses.  Physical comforts include the following: keeping the animal cry and clean, appropriate temperature, sufficient space to permit normal postural adjustments, avoid unnecessary physical restraint, prevent overcrowding, facilitate effective sanitation, and should meet the investigator’s research requirements.

Cats may be individually or group housed.  This will depend on the type of caging available, the temperament of the cats, and the potential effects on the research.

Environmental Enrichment is critical to the well being of cats.  The specifics will depend on the research project the animals are involved in, as well as the number of other cats in the housing environment.  Enrichment should include toys, scratching post/boxes, and food treats if possible.

  1. CONDITIONING

A conditioning program is designed to eliminate infectious agents and parasites and acclimate the animals to the laboratory environment.  Occasionally a program will hold cats for 7-14 days, but more successful programs hold cats for 30-60 days before proceeding to the next stage in the research.

Due to the potential of disease, random source cats should be individually housed for the first few weeks.  Panleukopenia will usually show clinical signs during the first week, however, respiratory viruses may take 2 weeks or more to manifest symptoms of disease.  Fleas, ear mites, and intestinal parasites must all be identified and treated at arrival.  Ideally, random source cats should be vaccinated and isolated until immunity develops.  It is critical for animal care staff to be aware of the potential disease signs and notify the Veterinary staff as soon as signs are noticed.   Once the cats have successfully completed the conditioning period they can be placed in community groups.

  Below is an example outline of a Conditioning program:

 Arrival Procedures
  1. Physical examination for immature, aged, ill, or those that fail to meet specific  research criteria.
  2. Weigh, sex, identify, and initiate individual health records.
  3. Initiate administration of a broad spectrum antibiotic for 10-14 days.
  4. Vaccinate for rhinotracheitis (FVR), calicivirus (FDV), and panleukopenia.
    Feline pneumonitis (FPN) and Chlamydia psitacci may also be given.
  5. Provide food and water.
Post-arrival procedures
  1. Dust or spray each cat with a topical insecticide
  2. Examine ears for ear mites and treat as necessary.
  3. Examine feces (parasites and ova).  Treat as necessary
  4. Monitor food and water intake daily
  5. Observe daily for signs of illness
Prerelease procedures
  1. Physical examination
  2. Examine feces (parasites and ova)
  3. Hematology and clinical chemistry exam as needed for specific research
General Considerations
  1. Newly received cats should be isolated as a group.  Precautions should be made to ensure safety of personnel, and transmission of disease from fomites and ventilation.
  2. Long-term cats should receive yearly vaccinations.
  1. COLONY MANAGEMENT
The prevention of disease and the production of healthy animals for research is the goal of the animal health care facility and its veterinary care staff.  Sound husbandry and preventive medical programs should minimize the need for diagnosis and treatment of disease in a colony.  Economic costs and the medical benefits of a preventive medical program must be considered when designing a management program.

Environment
As discussed previously in Housing, the environment must be kept clean and dry, the humidity and temperature must be controlled and monitored regularly.  Due to fecal-oral transmission of disease and parasites, cleanliness is a necessity.  The arrangement of cages will depend on the type of cats involved (males, females, nursery, kittens).   It will vary depending on the age and sex of the animals. Proper social environment is extremely important, this includes human contact. For an animal to be useful in a research project it must be socialized to humans.

Nutrition
The Animal Welfare Act requires that animals be fed clean, wholesome palatable food at least once daily from food containers that minimize contamination by excreta.  A good quality commercially available balanced cat food should be fed.  Nutrient requirements are outlined in the national Research Council document “Nutrient Requirements of Cats” (NAS-NRC, 1978), as well as a variety of other resources.  It will depend on the age of the cat as to the amount and timing of the feedings.  Most research facilities feed cats ad libitum, unless obesity or research requirements dictate otherwise.  Depending on the type of research and/or the condition of the animal, the requirements will vary, i.e. gestational requirements are significantly different than for an older male cat.

Clean fresh water should be available at all times, unless less is necessary for surgical preparation or for specific research projects.  The Animal Welfare Act requires  that water must be offered for a 1-hour period twice daily.

Immunization
A routine vaccination program should be instituted for long-term cats.  Short-term cats should be dealt with on an individual basis.  As stated previously, FVR, FCV should be given to all cats. FPN and Chlamydia may be given depending on the presence in the colony or in incoming animals. Vaccination against rabies is not generally warranted unless it is required for shipping regulations.

Parasite Control
Routine testing is important to detect parasites (internal and external).  This is a very important part of the preventive medicine program in a cat colony.  External parasites are easily controlled by sanitation and treatment with parasiticidal agents on a routine basis or after positive testing. The type of research may dictate the type of agent possible.  Direct fecal smears and fecal flotations should routinely be surveyed for internal parasites.  The appropriate treatment will be dictated by the results of the tests.

Parasite control depends on sanitation and appropriate therapies.

Record Keeping
Thorough and accurate record keeping is key to a successful management program.  All physical information, such as: size, conformation, abnormalities, growth rate, litter-mate information, behavioral disposition, maternal instinct, mating behavior, libido, gestational parameters, parturition information, lactation, kitten growth and health, medical history  should be recorded to assist in future colony and medical management.
  1. DISEASES OF CATS
Prevention of disease is the most important aspect of animal care, especially in a research facility.  Good husbandry practices and proper vaccination are key.  Vaccination of the common respiratory diseases is mandatory.  These include Viral rhinotracheitis (FVR) and feline calicivirus (FCV).  FVR may cause abortions in pregnant females.  This is thus extremely important in a breeding facility.  Panleukopenia virus (feline infectious enteritis) is relatively rare, but this is due to the efficacy of vaccination.  All kittens should be vaccinated.  Again, infection during pregnancy may result in abortions, still births or neonatal death and kittens, if they survive, may have cerebellar hypoplasia.

Incoming cats should be tested for Feline Leukemia Virus (FeLV).  This is extremely important if a breeding colony is in place or to be established, as FeLV may cause thymic atrophy and immunologic incompetence in the kittens.  This results in increased susceptibility to other diseases.  Once tested negative the cats may be vaccinated if the protocols for the research facility warrant.

Cats should also be tested for Feline Infectious Peritonitis (FIP) as this disease will have detrimental effects on breeding colonies and long-term research projects.  FIP is a coronaviral disease that may be asymptomatic, or cause upper respiratory disease, chronic weight loss, depression, and fever that is nonresponsive to antibiotic therapy.  The clinical syndrome varies widely depending on the organs affected.

Feline pneumonitis, which is caused by Chlamydia psittaci, causes a small percentage of the upper respiratory infections.  Many respiratory infections are caused by a combination of viral and bacterial agents, thus clinical differentiation is not easy.  Direct contact, fomites or aerosol droplets spread these diseases, thus the importance of quarantine for new animals.   A quarantine period for a minimum of 30 days and animals that are disease free for 2 weeks helps to decrease the potential for disease spread.   Diagnoses of disease potential and appropriate vaccination are important elements in keeping a facility free of disease.

Many cats also serve as a reservoir of Salmonella infections for other animals and the animal caretakers.  Newly arriving cats should also be screened for enteric salmonella, as this may result in a serious zoonotic problem.  Ringworm (Microsporum sp.) is also commonly found in random source cats.  These may be transmitted from cat to cat and cat to human.  Diagnosis and treatment are effective, but animals should be held in quarantine until cleared of the disease.  Only personnel with the proper protective clothing should handle positive animals.  All surfaces in the animal room should be treated, as the dermatophytes can persist in a dry environment for up to 13 months.

While in quarantine, cats should be screened and examined for internal and external parasites.  Appropriate therapies should be instituted.
  1. CARDIOVASCULAR DISEASE
Microcirculation Studies
The cat Sartorius muscle is especially appropriate for the study of microcirculation because it is thin, accessible, and the circulation can be well visualized. The cat Sartorius muscle permits alteration of arterial pressure to muscle by localized occlusion of the supply artery. The processes of vasodilation, hemorrhage, hyperemia, and stimulation as it relates to blood flow can be studied.

Cardiomyopathies
Since cardiomyopathy in cats closely resembles that in humans, the cat has been used as a model to evaluate new therapeutic approaches
  1.  ENDOCRINOLOGIC DISEASES
Diabetes Mellitus
Diabetic cats have proven extremely useful models for the study of Diabetes Mellitus. Diabetes Mellitus with amyloidosis of pancreatic islets occurs with significant frequency only in the cat and in man. Type 2 (non-insulin-dependent) diabetes mellitus constitutes up to 90% of all cases of diabetes mellitus in humans. In contrast to Type 1 (insulin-dependent) diabetes mellitus, where evidence supports an absolute insulin deficiency related to insulitis and islet cell destruction by a combination of viral and immunologic mechanisms, the intra-islet deposition of amyloid is a common islet alteration in human Type 2 diabetes. The diabetes mellitus-islet amyloid complex which occurs spontaneously in adult cats has many documented similarities to Type 2 diabetes mellitus in humans, and provides a model for further investigation into the sequential morphologic and biochemical alterations that occur in islets of individuals with this form of diabetes mellitus associated with aging.  Through the use of the feline model, more has been learned about the protein that decreases insulin production, thus the research may someday lead to a cure for diabetes.  Information about Cats with Diabetes (www.felinediabetes.com).
  1. HEMATOLOGICAL DISORDERS
Chediak-Higashi Syndrome (CHS)
This disease has been described in Aleutian mink, Hereford cattle, mice, killer whales, and cats. It is a disease characterized by inheritance as an autosomal recessive trait, dilution of the color of the hair and eyes caused by enlargement of the melanin granules in the hair and ciliary processes of the eye, and includes an increased susceptibility to disease as a prominent feature, probably related to the increased size of the granules in the leukocytes. Sufferers also tend to have hemorrhagic tendencies due to a platelet storage pool deficiency. In the cat, it is present in Blue-smoke Persians with yellow rather than the more typical copper-colored irises. The genetic, clinical, and pathological manifestations of CHS in cats is remarkably similar to the syndrome in humans. In addition, CHS cats make an appropriate animal model to evaluate hemostatic capabilities of transfused platelets.
  1. IMMUNOLOGIC DISEASES
Acquired Immunodeficiency Syndrome:  Feline AIDS  & Human AIDS
Feline AIDS is a virus similar to the human AIDS disease, and both have similar symptoms.  These include:  swollen lymph nodes, extreme weight loss and respiratory infections. Because of the research using cats as a model, scientists have been able to develop a vaccine for feline leukemia.  The hope and further study is that this breakthrough can provide a model for the development of a vaccine against human AIDS. Severe progressive immunodeficiency syndrome can be induced experimentally with a molecularly cloned isolate of feline leukemia virus (FeLV-FAIDS). Persistent viremia, lymphopenia, progressive weight loss, persistent diarrhea, enteropathy, and opportunistic infections characterize the resultant disease syndrome. The onset of clinical immunodeficiency disease is prefigured by the replication of the FeLV-FAIDS variant virus in bone marrow and other tissues.

The FeLV-FAIDS system can be used to evaluate antiviral agents which act on steps in the replication cycle which are conserved among retroviruses (e.g., reverse transcriptase, protease, assembly). The persistence and magnitude of viremia serves as a useful parameter in antiviral studies because it can be easily measured, presages the eventual development of immunodeficiency, and provides a convenient indicator of therapeutic efficacy either in preventing de novo FeLV infection or in reversing or ameliorating established infection. The FeLV model, therefore, can be used to assess rapidly experimental single agent or combined antiviral therapies for persistent retrovirus infection and disease.

Feline immunodeficiency virus infects the CNS and results in predictable pathophysiology strikingly similar to that seen with HIV-1 infection of humans. The observed pathophysiology is mimicked in several physiologically assessed modalities, further supporting the validity of the feline model. Peripheral and control evoked potential findings and the occurrence of the sleep architecture changes in both cat and human disease provide an intriguing focus for further investigation. Although structurally diverse in an absolute sense, FIVand HIV-1 share basic structural features and commonalties of their life cycle. It is likely that by understanding the common mechanisms by which these lentiviruses influence CNS function, a more complete understanding of the neurological deficits seen in HIV-1 infected patients will be obtained. The cat model is particularly valuable for study of CNS disease, since it allows detailed analyses of events during the acute phase of infection, under circumstances in which the nature and timing of the infection are carefully controlled. The availability of molecular clones for mutational analysis will facilitate mapping of genomic regions critical to the perturbation of CNS function. It is suggested that development of intervention  strategies in the cat model will yield treatment modalities directly applicable to HIV-1 infection of humans.

Monoclonal Gammopathies
In man, patients with monoclonal gammopathies such as multiple myeloma or Waldenström’s macroglobulinemia frequently have large quantities of homogenous immunoglobulins in their sera. Spontaneous, functional plasma cell dyscrasias have also been encountered with in the dog and in the cat. Studies of the pure proteins isolated from such animals led to a clearer understanding of the classes of canine and feline immunoglobulins and to a fuller appreciation of the structural relationships between theses proteins and their counterparts in man.

Mucopolysaccharidosis
In the April 1987 issue of Lab Animal, there is an article describing the formation of a National Referral Center for Animal Models of Human Genetic Disease. In the article, there is a description of this feline model. This model has been shown to be a counterpart of MPS VI (Maroteaux-Lamy syndrome) in humans.  In the classic form of MPS VI in humans, affected individuals exhibit growth retardation, facial abnormalities, corneal clouding, skeletal abnormalities, and heart valve defects. The most severely affected human patients do not survive past their twenties. The clinical and pathologic findings in Siamese Cats are rather similar and include growth retardation, broad faces with short ears, and skeletal abnormalities.  Mentation is difficult to assess in animals; however, there have been no indications in any of the affected cats of deficits comparable to those defining mental retardation in man. The pathogenesis in cats and humans is essentially similar: it is a single gene mutation, inherited as an autosomal recessive disorder, which results in an activity deficiency of a lysosomal enzyme called arylsulfatase B.  Without this enzyme, a specific compound, dermatan sulfate, cannot be broken down, so it accumulates in cells and overflows into the blood and urine.  As the condition progresses, different organs are affected, which results in the clinical signs.  One of the advantages of this model is its suitability for testing new modes of therapy for MPS.  Such methods include enzyme manipulation/replacement, bone marrow transplantation, and gene therapy.  Other animal models of MPS currently under investigation are domestic shorthair cats (MPS-1) and mixed breed dogs (MPS VII).
  1. ORAL/ EAR / NOSE / THROAT
Hearing Loss
As a result of exposure to high level noise, humans and cats may have resulting. Because of this similarity, researchers have been able to study the effects of noise on cats and apply it to humans.

Otitis Media
Otitis media is an inflammation of the middle ear, which may or may not be of microbial origin. The clinical findings in cats resemble those seen in humans.  Twenty-four hours after inoculation with Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, or Pseudomonas aeruginosa, the ear drum appears reddened and bulging with the disappearance of its landmarks. Occasionally a perforated eardrum is seen 2 to 3 days after inoculation. The causing organisms can be seen in the inflammatory exudate. The lining of the middle ear undergoes metaplasia in a respiratory-type epithelium. This model has been especially useful in those cases where the eustachian tube remains patent.

Pediatric Intubation Labs
Kittens are used to teach intubation techniques to physicians and other health care personnel. This model is used because the size of the kitten is similar to that of premature newborn babies.

Dental disease
Studies examining the causes and treatments for dental caries and destructive periodontitis have successfully been conducted using the cat as a model.
  1. NEUROLOGIC DISORDERS
A great deal has been learned about the feline sensory system. It is because of similarities between the neurological system of the cat and human, that cats have been used as models.  The research with feline models has successfully led to the understanding of the function of neurons, the chemical transmission of nerve impulses, specific functions of nerve cells, functional organization of the brain and mechanisms of nerve impulse transmissions.  The cat makes an excellent model for studying many aspects of the nervous system, some of which are described below.

Feline GM1 Gangliosidosis
Cats with this disorder seem to be the best model yet discovered for the human condition of the same name. In both humans and cats, the CNS degeneration and deficiency of ß-galactosidase, with associated neuronal accumulation of GM1 gangliosides and visceral accumulation of proteoglycans, appear to be related to an autosomal recessive gene. The cat has much to recommend it as the model of choice in this case: 1) availability of established research colonies; 2) extensive characterization of the feline disease; 3) remarkably close analogy with the diseases in children; 4) high reproductive capacity in cats; 5) ease of maintenance and handling of  cats; 6) body size which facilitates clinical observations, surgical manipulations, testing and treatment procedures, and availability of reasonable volumes of tissues and body fluids; and 7) unrivaled position of cats as the favorite species for neurological research, which leads to a vast repository of data on the feline nervous system. 

Neuroprosthesis Development
The dynamic performance model of the medial gastrocnemius and soleus muscles of the cat are used to generate isometric force at its tendon and when transmitting that force across the joint. The model is useful in the design of a neuromuscular prosthesis, using electrical stimulation of the muscle nerves, as a rehabilitation procedure for paralyzed patients due to spinal cord injury.

Sphingomyelin Lipidosis (Niemann-Pick Disease)
In the human, the myoclonic seizures, ataxia, intellectual deterioration, hepatosplenomegaly, anemia and premature death are due to a deficiency of sphingomyelinase which normally splits the phospholipid sphingomyelin into ceramide and phosphocholine. The feline condition most closely mimics the human condition; the clinical, morphologic, and biochemical features of the human and feline diseases are virtually identical. The earliest recognized clinical features of feline NPD are retarded growth and occasional knuckling over in the rear legs. As the disease progresses, there is increased incoordination in the rear limbs, splaying of legs, and involvement of forelimbs. Later there is depression, apparent blindness, anorexia, and continuous bobbing of the head. Eventually total paresis and anorexia lead to death. One alteration in human NPD not yet found in affected cats is the macular "cherry red spot" seen ophthalmoscopically. Although the human disease has been established as having an autosomal recessive mode of inheritance, the genetic basis for the disease in Siamese cats is not yet fully established.

Spina Bifida
The spontaneous occurrence of this condition in the Manx cat has been offered by many investigators as a model through which to study the similar condition in humans. Detectable amounts of a-fetal protein in amniotic fluid have been reported in human pregnancies with neural tube defects. Similar detection has been verified in the Manx cat with neural tube anomalies. The clinical syndrome varies and can include: megacolon, urinary incontinence with secondary predisposition to urinary infection, locomotor disorders, uterine inertia and chronic cystitis, along with the wide variety of bony anomalies. It appears to be an autosomal dominant trait with incomplete penetrance. The near absence of hydrocephalus and other CNS lesions in the cat model dims total homology, but this is the best known and most homologous model to date.

Spinal Cord Injuries
Spinal cord injury continues to be a major medical problem for humans, affecting between 250,000 and 350,000 Americans with 6000 to 10,000 new cases occurring each year. In the past few years, much improvement has been made in the quality of life of spinal cord-injured patients through the use of assisted locomotion and functional electrical stimulation-interventions that were developed and tested in control and/or spinal cord-injured animal models, especially the cat. One of the more exciting observations of chronically spinalized cats from a rehabilitative viewpoint is that the locomotor capability of the hind limbs of spinally transected mammals 1) can improve with practice of rhythmic movement, i.e., trained to walk on a treadmill and 2) is lost when cats are trained statically, i.e., trained to stand.  Thus it appears that the mammalian spinal cord can learn and forget. Based on the similarities of the clinical complications as well as the physiological adaptations of the paraplegic cats and humans, the chronic spinal cats serve as an outstanding model for developing optimal rehabilitative strategies for spinally injured patients.

Stroke
Studies investigate the relationships among neurological deficits, changes in the electroencephalogram, and morphological damage over a one week period following temporary occlusion (2 hours or less) of the middle cerebral artery in the cat.  This stroke model in the cat has provided important data concerning the restitution of brain function following chronic focal ischemia.

Visual Disorders
Studies using cats as models have allowed researchers a better understanding of ophthalmic disorders such as Amblyopia ("lazy eye") and Strabismus ("cross-eye") – which occur in many animals and humans. Glaucoma and cataract surgery has also progressed due to the contribution that cats have made as models.

  1. PARASITIC
Filariasis
The responses of cats to Brugia parangi, which parasitizes them in nature, mimic those of humans to Brugia malayi and Wuchereria bancrofti, the causative agents for Elephantiasis, in many important respects. In both host-parasite relationships, the adult worms are found in the lymphatics and microfilariae circulate in the blood.  Infections are often very long lasting in both human and feline filariasis. Some people who have lived in an endemic area for some years eventually become amicrofilaremic, as do some cats if repeatedly infected with larvae. It is likely that many of the features of the relationship between host and parasite that can be studied in cats infected with B. parangi also apply to humans, but for a variety of practical reasons cannot be demonstrated in humans.

Helocobacter pylori Infection
H. felis is supposed to be adapted to life in the gastric mucosa of the cat in the same manner as has been observed for H. pylori in the human gastric mucosa. The fact that H. felis induces an acute inflammatory response followed by a chronic active inflammation makes this model attractive as it can be used to resemble H. pylori infection/gastritis.

Toxocariasis
Toxocariasis is a parasitic infection caused by roundworms and while roundworms are most common in dogs, they may also be found in cats. Although the infection usually doesn't cause symptoms in adults, it can cause a variety of problems in children, including allergy-like signs and symptoms such as, hives, muscle pain, fever, abdominal pain, respiratory problems (coughing, wheezing).  In rare cases it can lead to swelling of organs, central nervous system and partial blindness.  Again, prevention is key. Checking feces for eggs and treating appropriately, washing hands, and not allowing feces to remain (in sand, soil, lawns) will effectively eliminate roundworm populations.
  1. TOXOCITY
Methylmercury Toxicity (Minamata Disease)
Since methylmercury is an extremely toxic compound and lesions often are irreversible, early detection of disease when methylmercury poisoning is suspected and satisfactory methods of treatment must be developed in animal studies. Since the cat is more susceptible to methylmercury than man, this species can be useful as a sentinel animal to avert possible impending disasters. Cats becoming ill in northwestern Ontario, Canada in 1975 alerted authorities to look for a methylmercury toxicity problem, which they promptly found before any human illness had occurred. Cats became ill prior to the outbreak in Minamata, Japan, in the 1950s, but it went unrecognized until after-the-fact.
  1. MISCELLANEOUS / INFECTIOUS
Toxoplasmosis
Approximately 4500 infants are born with congenital Toxoplasmosis annually in the United States. This disease is carried by cats and spread through infective stools and ground.  Virtually all research on this infection has been done using the cat as a research model, and the goal is to develop treatments and protective measures.

Toxoplasmosis (TOX-o-plaz-MO-sis) is a disease that can come from cats, but people are more likely to get it from eating raw meat or from gardening (areas where infected cats have defecated).  Toxoplasmosis is sometimes called litter box disease and results from contact with a parasite present in cat feces, soil or undercooked meat. Most cats do not exhibit signs or symptoms of infection, rather family members will have symptoms resembling the flu (swollen lymph glands, fatigue, fever, headache), although there may be no signs. 

Prevention is key, thus don’t feed cats undercooked meat or to allow potential exposure to infected animals (for pets this means keeping them indoors).  Pregnant women should allow others to clean litter box due to the severe cost if infected (miscarriage, premature births and mental retardation in newborns). Fortunately, Toxoplasmosis can be treated, even during pregnancy.

Carcinogenesis
Cats have been used to evaluate potential therapeutic techniques in the treatment of lymphosarcoma, adenocarcinoma, malignant lymphoma, multiple myeloma, squamous cell carcinoma, acute lymphoblastic leukemia, aplastic anemia, and hypercalcemia of malignancy.

Because of its similarity to human breast cancer, feline mammary carcinoma continues to be an important model for the evaluation of new forms of therapy for breast cancer. 

Investigative Models
Because dietary-induced atherosclerosis also occurs in cats, this species has been used as a model of atherosclerosis in humans.Cats are extensively used as investigative models in neuroanatomy, neurosurgery, neurology, neurophysiology, toxicology, and reproductive physiology. The fact that adult cats are fairly uniform in size with regard to the head, skull, and brain makes the placement of neurologic probes a more precise procedure, thus making cats a better model for this type of research than other species.
  1. NORMAL FELINE PHYSIOLOGIC DATA
 TABLE 1.  Physiologic Data for Feline
Parameter All Breeds, Normal Range
Weight, adult males, kgs. 3.5
Weight, adult females, kgs. 2.5
Birth weight, gms. 110-120 gms
Female, onset of puberty 5-12 months
Male breeding age, time of onset 36 weeks

Estrous cycle

Polyestrus,   January – October,  Lasts 2-3 weeks, Estrus duration is 3-6 days
Gestation, days 58 – 65
Ovulation Induced
Litter size 3 to 5 kittens
Weaning age, weeks 3-8 weeks
Breeding life 6-8 years

Breathing rate/minute

26 avg.

Heart beats/minute, adult 110 – 140
Blood Pressure (Systolic/Diastolic) 120mm Hg / 75mm Hg
Body temperature 101.5 o F   (38.6 o C avg.) -- Range: 38.1 o C – 39.2o C
Feed consumption (avg.) 24 gm/ per 1 kg. of body weight
Water consumption Ad Libitum
  1. ZOONOTIC DISEASES

Zoonotic diseases are those diseases that can be transmitted between people and another species. People are more likely to contract ailments from other people, but it does occur between cats and people.  Most diseases pose minimal threat, unless the person is immunologically compromised, has an immature or compromised immune system (infants, AIDS patients, elderly, etc.) which makes them more susceptible to infection.  Hygiene and common sense are the best methods of prevention. These include:
 
  • Washing hands before and after handling cats, wearing gloves when handling feces
  • Perform fecal exams regularly and treating appropriately
  • Keep vaccinations current (Rabies)
  • Maintain appropriate flee and tick control
  • Feed cats cooked or commercially processed food
  • Keep litter boxes clean of fecal material (do not let it build up)
Transmission usually occurs from direct contact with secretions or excretions (saliva, feces) from an infected cat, but it may also be spread through contaminated food, water, or transmitted by parasites or another animal. Common Zoonotic Diseases (Details found in other sections of this manuscript or in the lecture on Zoonosis): 
Bacterial Infections:
  • CSD (Most Common Zoonotic Disease of cats) --- Cat Scratch Disease, bartonellosis, benign inoculation lymphoreticulosis, nonbacterial regional lymphadenitis
  • Bites and Scratches (Pasteurella sp. (m/c),  Clostridium tetani, Streptobacillus
  • moniliformis, Spirillum minus)

Parasitic Infections:

  • Fleas (most common external parasite of cats):  Result in itching and inflammation, but serve as vectors for CSD and others
  • Roundworms and Hookworms.
Fungal Infections:
  • Ringworm:  usually appears as a dry gray, scaly patch on the skin.  In humans it is usually red, round and itchy with a ring of scale around the edge.
Protozoal Infections:
  • Cryptospoidiosis
  • Toxoplasmosis
  • Giardiasis:  causes diarrhea in cats and people. 
Viral Infections:
  • Rabies
  TABLE 2 - Selected Feline Zoonotic Diseases
Disease in Humans Agent Mode of Transport
Rabies Rabies virus Direct
Psittacosis Chlamydia psittaci Direct
Q-Fever Coxiella burnetti Inhalation or Ingestion
Leptospirosis Leptospira spp. Direct
Plague Yersinia pestis Direct or Indirect
Campylobacteriosis Campylobacter jejuni Direct
Salmonellosis Salmonella spp. Direct
Tularemia Francisella tularensis Indirect (tick)
Mycoses (Ringworm) Microsporum spp. , Trichophyton spp. Direct or Indirect
Toxoplasmosis Toxoplasma gondii Reservoir
Strongyloidiasis Strongyloides spp. Oral or Transcutaneous
Larval Migrans (visceral) Toxocara cati, leonina Direct
Larval Migrans (cutaneous)  Ancystoma braziliense, duodenale, Uncinaria stenocephala, Necator Americanus Direct
Scabies Sarcoptes scabiei Direct
Mange Notoedres cati Direct
Dermatitis Cheyletiella spp. Direct or indirect via bedding
Dermatitis, vector of Hymenolepis diminuta, Dipylidium caninum Ctenocephalides felis (cat flea) Direct
Cat Scratch Disease (CSD), Benign inoculation lymphoreticulosis, nonbacterial regional lymphadenitis Mycobacterium Direct
Bites and Scratches Pasteurella sp. Clostridium tetani, Streptobacillus moniliformis, Spirillum minus Direct
Hypersensitivity Dander, saliva, urine Direct or indirect
  1.   REFERENCES  & WEB SITES

Aclaud GM et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet. 2001:28:92-95.

Albarellos GA, Ambros LA, Landoni MF.  Pharmacokinetics of levofloxacin after single intravenous and repeat oral administration to cats.   J Vet Pharmacol Ther. 2005;28,4:363-9.

Animals in Research. Connecticut Medicine. 1989;53(8):483-488. 

Center SA, Randolph JF, Warner KL, McCabe-McClelland J, Foureman P, Hoffmann WE, Erb HN.  The effects of S-adenosylmethionine on clinical pathology and redox potential in the red blood cell, liver, and bile of clinically normal cats.   J Vet Intern Med.  2005;19,3:303-14.

Cowles, BE, Meyers, KM, Wardrop, KJ, et al.   Prolonged bleeding time of Chediak-Higashi cats corrected by platelet transfusion. Thromb Haemost. 1992;67(6):708-712. 

Denham, DA, Medeiros, F, Baldwin, C, et al.   Repeated infection of cats with Brugia parangi: parasitological observations. Parasitology. 1992;104(3):414-420. 

Denham, DA and Fletcher, C.  The cat infected with Brugia parangi as a model of human filariasis. Ciba Found Symp. 1987;127:225-35. 

Engstrand, L.  Potential animal models of Helicobacter pylori infection in immunological and vaccine research. FEMS Immunology and Medical Microbiology. 1995;10:265-270. 

Federlin KF, Jahr H, Bretzel RG. Islet transplantation as treatment of type 1 diabetes: from experimental beginnings to clinical applications. Exp Clin Endocrinol Diabetes 2001:109: 73-83. 

Franz, BK, Shepherd, RK, Clark, GM.  Otitis Media. Comparative Pathology Bulletin. 1991;23(1):2-6. 

Gingras G, Mitchell DE, Hess RF.  Haphazard neural connections underlie the visual deficits of cats with strabismic or deprivation amblyopia  Eur J Neurosci.  2005;22:119-24. 

Grant S, Hilgetag CC.  Graded classes of cortical connections: quantitative analyses of laminar projections to motion areas of cat extrastriate cortex.  Eur J Neurosci.  2005;22,3:681-96.

Health Benefits of Animal Research. Ed. by WI Gay. Foundation for Biomedical Research, Washington, DC. 1984: 41-64. 

Hoover, EA, Zeidner, NS, Perigo, NA.  Feline Leukemia virus-induced immunodeficiency syndrome. Intervirology. 1989;30 Suppl 1:12-25. 

Komatsumoto, S, Greenberg, JH, Hickey, WF, et al. Clinicopathological observations in middle cerebral artery occlusion in the cat. Neurological Research. 1995;17:120-128. 

Lewis, SM and Carraway, JH.  Large Animal Models of Human Disease. Lab Animal. January, 1992;:22-29. 

Matteucci D et al. AIDS vaccination studies using feline immunodeficiency virus as a model: immunization with inactivated whole virus suppresses viraemia levels following intravaginal challenge with infected cells but not following intravenous challenge with cell-free virus.  Vaccine.  1999:18:119-130. 

Narayanaswamy M et al. Animal models for atherosclerosis, restenosis and endovascular graft research. Vasc Interv Radiol. 2000:11: 5-17. 

Overeem S, Mignot E, van Dijk, Lammers GJ.  Narcolepsy: clinical features, new pathophysiological insights, and future perspectives. Journal of Clinical Neurophysiology.  2001:18:78-105. 

Roy, RR, Hodgson, JA, Lauretz, SD, et al.  Chronic spinal cord-injured cats: surgical procedures and management. Lab Anim Sci. 1992;42(4):335-343. 

Shue, G, Crago, PE, and Chizeck, HJ.  Muscle-joint models incorporating activation dynamics, moment-angle, and moment-velocity properties. IEEE Transactions on Biomedical Engineering. 1995;42(2):212-23. 

Walter JS,Wheeler JS,Fitzgerald MP,McDonnell A,Wurster RD.  Chronic instrumentation with model microstimulators in an animal model of the lower urinary tract.    J Spinal Cord Med.  2005:28,2;114-20. 

X i MC, Morales FR, Chase MH.  Effects of sleep and wakefulness of the injection of hypocretin-(orexin-A) into the laterodorsal tegmental nucleus of the cat.  Brain Res.  2001:901:259-264. 

Zhou, BH, Solomonow, M, Baratta, R, et al.  Dynamic performance model of an isometric muscle-joint unit. Medical Engineering and Physics. 1995;17(2):145-50. 

Web Sites: 

http://www.kids4research.org/info_pages/animals.htm

http://www.fbresearch.org/Education/Links.htm 

http://www.fbresearch.org/Education/pdf/DogsAndCats.pdf

http://www.cdc.gov/healthypets/animals/cats.htm

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Table of Contents

Sources of Cats

Criteria for Selecting Experimental Animals

Housing
Conditioning
Colony Management
Diseases of cats

Cardiovascular Disease
Microcirculation Studies
Cardiomyopathies

Endocrinologic Diseases
Diabetes Mellitus

Hematologic Disorders
Chediak-Higashi Syndrome (CHS)

#IMMUNOLOGIC
Acquired Immunodeficiency Syndrome (AIDS)
Monoclonal Gammopathies
Mucopolysaccharidosis

Oral/Ear/Nose/Throat
Hearing Loss
Otitis Media
Pediatric Intubation Labs
Dental Disease

Neurologic Disorders
Feline GMI Gangliosidosis
Neuroprosthesis Development
Sphingomyelin Lipidosis (neimann-Pick Disease)
Spina Bifida
Spinal Cord Injuries
Stroke

Parasitic
Filariasis
Helocobacter Pylori Infection

Toxicity
Methylmercury Toxicity

Miscellaneous
Toxoplasmosis
Carcinogenesis
Investigative Models

Normal Feline Physiologic Data
Table 2. Physiologic Data for Feline

REFERENCES

 
 
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 Revised 09/27/2011