III    The Laboratory Ferret

Reading Assignment:  in-text links

Study Guide

1. Taxonomy:
   
   The laboratory and pet ferret is a domestic animal descended from the wild European polecat (Mustela putorius).  The taxonomic classification of the domestic ferret is:

   Kingdom Animalia
   Phylum Chordata
   Class Mammalia
   Order Carnivora
   Family Mustelidae
   Genus Mustela
   Species Mustela putorius furo

   Mustela is a derivative of the Latin mus (mouse), based on the ferret's mouse-hunting abilities.  Putorius is from Latin putor (stench) and furo means thief.  The ferret is a smelly mouse-catching thief!
   
   Ferrets are members of the Order Carnivora, along with dogs, cats and other meat-eating animals.  They belong to the family Mustelidae, which also includes mink, weasels, skunks and otters.  All of the mustelids have well-developed anal scent glands, used for defense and communication.
   
   The natural color of the ferret is sable or fitch (see below).  A sable ferret is tan with a dark mask, legs and tail.  Albino ferrets are frequently used in research.  Over thirty color variations are recognized in pet ferrets, including cinnamon, Siamese and silver.
    
    

2. History of the Ferret:

   Ferrets were domesticated over 2000 year ago.  During the Middle Ages, ferrets were used for hunting rabbits and for rodent control, a practice that continues in Great Britain.

   Ferrets were imported into the United States in the in the 1880s for use in hunting.  Most states banned hunting with ferrets in the early 1900s.  Pet ferret ownership is regulated by state Fish and Wildlife or Conservation Departments with some states banning ownership and some allowing ownership only by permit.  Regulation, where it exists, is intended to prevent decimation of rabbit populations if ferrets escape.

   The slender ferret body and its love of tunnels created a role for ferrets as transporters of wires and cables.  Boeing used ferrets to run wires through tight spaces during aircraft assembly.  Mechanical methods have since displaced the ferret from this job.

   Ferrets have been used as biomedical models since the 1930s, particularly in the United States, where large-scale breeding facilities produce thousands of healthy ferrets.  The primary supplier of laboratory and pet ferrets in the U.S. is Marshall Farms.  They spay or castrate and descent their ferrets before selling them, marking their right ears with two black tattooed dots.

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1. The Role of the Ferret in Research:

   One of the earliest uses of ferrets was research on the influenza virus.  Ferrets, like people, are susceptible to this virus and exhibit similar signs.  Flu vaccine manufacture depends upon the ferret to test vaccine efficacy.

   Ferrets are also used to study canine distemper virus.  This disease in ferrets has a high morbidity (number of animals sickened) and mortality (number of animals that die).  The ferret was instrumental in the development of canine distemper vaccine for dogs and is used to assess the effectiveness of vaccines.

   They are also important models for gastro-intestinal problems including ulcers caused by the bacterium Helicobacter (which is implicated in ulcers in people) and vomiting (ferrets are the model of choice for studying how vomiting occurs and how to prevent it).

   Neuroendocrinology studies of breeding behaviors utilize the ferret.  Because of the similarity of the metabolism and physiology of the ferret to man, the ferret can be used to study the toxicologic properties of substances.

   Bone marrow studies are performed on the ferret because excessive secretion of estrogen by intact female ferrets may suppress the bone marrow, causing severe anemia.
   
   

2. Ferret Statistics:

   Criterion	Ferret
   Life Span	5 - 8 years
   Adult Size	1 - 2.5 kg
   Temperature	100.0 - 104.0° F
   Pulse	180 - 250 bpm
   Respirations	33 - 36 rpm
   Estrous Cycle	Induced Ovulator
   Gestation	42 days
   Weaning Age	6 weeks

5. Anatomy and Physiology of Ferrets:

   The ferret has a long slender body with short legs, well-adapted for hunting down rabbit holes.  Its spine is very flexible and its neck is long and thick.  The feet have unretractable claws, like rabbits and dogs.

   A ferret shows seasonal fluctuations in weight and hair coat.  Ferrets lose body fat in the summer and gain it again as winter approaches.  The weight change is most dramatic in intact male ferrets, with the winter weight up to 40% greater than the summer weight.  The fur is molted in spring and fall;  subtle or dramatic changes may occur in mask configuration and hair color and length.

   The ferret spleen varies greatly in size, depending upon the ferret's health and age.  A spleen that can be palpated may be normal in an individual ferret, or it may be associated with lymphosarcoma, a common neoplastic disease of ferrets.

   Ferrets are carnivores, with simple monogastric stomachs and no cecum.  The teeth are all closed-rooted.  Ferrets have canine teeth; the upper canines can extend beyond the chin and may fracture them from chewing objects.

Ferrets have poorly developed sweat glands and are prone to heat exhaustion.  Their skin is thick, especially over the neck and shoulders.  They have a pair of large anal glands that produce secretions that are less potent than those of the closely-related skunk;  these glands are usually surgically removed when the ferret is spayed or neutered.  Sebaceous glands throughout the skin produce a persistent musky odor that is not affected by removal of the anal glands, but is somewhat alleviated by spaying or neutering.  Frequent bathing with a shampoo for kittens may also decrease the odor.

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5. Ferret Reproduction:

   Ferrets exhibit sexual dimorphism, and the male ferret is approximately twice the size of the female.  Both male and female ferrets have nipples.

   The female ferret is a jill.  She is a photo-dependent induced ovulator, normally breeding from March to August.  Estrus can be recognized by swelling of the vulva, and estrus will continue until she is bred.  If fertilization does not occur, pseudocyesis may result.

   If a female ferret is not bred, she may remain in estrus for up to six months.  The high level of estrogen associated with prolonged estrus may result in leukopenia (decreased number of white blood cells) and aplastic anemia (a severe deficiency of red blood cells due to bone marrow depression).

   After a gestation of 42 days, seven to fourteen altricial kits are born.

   The male ferret is a hob.  He has a J-shaped os penis (bone), which makes urinary catheterization difficult.  His breeding season is from December to July; during this time, his testes increase in size and then shrink afterwards.  Neutering decreases the adult size of hobs.  Intact male ferrets produce more sebaceous secretions than females or neutered males; this can result in a stronger body odor and yellow discoloration and oiliness to the fur.

   A monogamous mating system is frequently used for ferrets.
   
   

6. Ferret Temperament:

   Ferrets are active, good-natured and playful.  They are extremely inquisitive and will escape from any cage and hide anywhere.  

   The ferret likes to burrow, and will hide under rugs and recliners in the home, sometimes resulting in their injury when the rug is stepped on or the recliner is closed.  They will chew anything and everything, which may cause gastrointestinal obstructions.

   Ferrets are very vocal;  they chuckle and giggle while playing, whine when ill or upset and hiss when angry.
   
   

7. Ferret Technical Procedures:

   Ferrets can be restrained by scruffing at the back of their neck, suspending all four feet off the table.  This is the restraint method their moms used, and they typically become limp and don't struggle when held in this manner.  They can also be grasped like a sausage, supporting their hindquarters.  Feeding Nutrical®, a nutrient paste, while performing minor procedures may distract the ferret's attention from the activity.

Physical appearance is a poor choice for identification due to seasonal changes in coat.  

Blood can be collected from many veins, including the jugular, cephalic (front leg), saphenous (hind leg) and caudal (tail).  Cardiac puncture can be used to collect large volumes of blood from an anesthetized ferret;  this is a terminal procedure and used only in research.

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5. Ferret Husbandry:

   Ferrets need escape-proof cages with solid or wire flooring.  They like to sleep in dark enclosed spaces, so nest boxes or pet-trade hammocks are beneficial.  Ferrets are readily litter trained.  

   The optimal temperature range for ferrets is 40 - 65° F.  Temperatures in excess of 90° F may result in heat stroke.  Humidity should be between 45 - 55%.

   Ferrets are carnivores and need high quality meat protein.  Fiber should be minimized in their diet.  Ferrets also need more fats than rodents or rabbits;  deficiencies may result in a dull, dry hair coat.  Liquid fatty acids, meat fat or cooked egg yolk can be used as a supplement.  Commercial ferret pellets are available and should be used; high quality cat food may be fed if necessary.

   Fasting should precede medical procedures because ferrets vomit readily;  however, food withholding should not exceed six hours.  Hungry ferrets are difficult to handle and, if an insulinoma (insulin-producing tumor) is present, fasting may cause hypoglycemia, seizures and coma.

   Ferrets love to play in water.  A water bottle or automatic watering system should be used.  If an open bowl is utilized, it should be difficult to turn over by playing ferrets.
   
   

6. Ferret Health and Disease:

   Canine distemper has an extremely high morbidity and mortality in ferrets.  Ferrets have been used as models for canine vaccine development.  A distemper vaccine has been approved for use in ferrets.

   Humans and ferrets share the same influenza virus and can infect each other.  

   Ferrets are susceptible to rabies.  Vaccines approved for use in ferrets are available.  Many states require rabies-suspect ferrets to be euthanized (humanely killed) and tested for infection, although some states have recently allowed quarantine and observation of vaccinated ferrets.

   Jills may develop a number of reproductive problems, including pyometra (infection of the uterus), mastitis (infection of the mammary glands) and anemia from estrogen-associated bone marrow toxicity.

   Ferrets may be infected with the canine heartworm, Dirofilaria immitis.  This worm is transmitted by infected mosquitoes, causing coughing, dyspnea (difficult breathing), pulmonary congestion and sudden death.

   Insulin-secreting tumors (insulinomas) are common tumors of ferrets and result in hypoglycemia weakness, depression and convulsions.  Lymphosarcoma is the most common hematopoietic (blood-cell associated) cancer, resulting in neoplastic changes in lymphocytes and lymph nodes.

   An important disease in ferrets is adrenal-associated endocrinopathy (AAE) or ferret adrenal disease.  The adrenal glands have many functions, including regulation of sex hormone secretion.  Benign tumors of this gland cause hypersecretion of reproductive hormones.  The etiology (cause) of AAE is unknown, although early neutering, diet and inbreeding have been suggested as possible causes.  A characteristic sign of adrenal disease in ferrets is bilaterally symmetric alopecia (hair loss), beginning at the base of the tail and progressive cranially, but not including the head, neck or front legs.  In jills, swelling of the vulva, vaginal discharge and pyometra may occur.  Males exhibit dysuria (difficult urination).  Behavioral abnormalities include increased sexual aggressiveness (marking and mounting) and fighting may occur.  Longstanding cases may result in anemia (due to estrogen), muscle wasting and lethargy.  Treatment is typically surgical removal of the affected adrenal gland (usually the left);  complete recovery is usual.

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IV  Laboratory Swine

Reading Recommendations:  In-text links.

1. Taxonomy:

   Swine belong to the Order Artiodactyla.  Artiodactylids are cloven-hooved animals, with the third and fourth toes supporting the animals weight.  Other animals in Order Artiodactyla are cattle, sheep and deer.  

   Porcine is an adjective used to describe pigs.

   The complete taxonomic classification of the domestic pig is:
   
       Kingdom Animalia
       Phylum Chordata
       Class Mammalia
       Order Artiodactyla
       Family Suidae
       Genus Sus
       Species  Sus scrofa domesticus
   
   

2. History of Swine:

   Swine were domesticated over 3000 years ago.  They have been used in research since Erisistratus demonstrated the flow of air in the trachea of swine in 300 BC.  Miniature pigs were developed in the United States in the 1950s to create research swine of more manageable size.
   
   

3. The Role of Swine in Research:

   Swine are increasingly used in research.  Humans and swine have similar anatomy, physiology, biochemistry and pathology.  We respond to drugs in the same way.  We have similar lung size and functional capacity, analogous renal and pancreatic physiology;  we are both monogastric omnivores and our skin is of the same thickness and porosity.

   The pig's short reproductive cycle, ease of breeding, large litter size, diverse gene pool and early maturity contribute to its usefulness in the lab.  Pig usage in research has increased over the last several years because they are a nonrodent alternative to the often more expensive and more ethically objectionable dogs and primates.

   Some uses of swine in research include:

   • The study of vonWillebrand's disease (a coagulation disorder of man and dobermann pinschers)
   • The study of type II diabetes (swine have also be used as a source of natural insulin)
   • Development of dermal motion sickness patches (using the pig's hairless abdominal skin, which is analogous to human skin in texture, permeability and thickness)
   • The study of the relationship between stress and hypertension
   • Development and practice of microsurgery techniques on the urethra and oviducts
   • Fetal surgery (because swine and human neonates are at a similar development stage)
   • Organ transplantation research
   • Source of heart valves, livers and other structures for xenotransplantation (transplantation of animal cells and tissues into humans)
   • Study of the role of diet, exercise and treatment of osteoporosis in older sows
   • Study of atherosclerosis and the role of dietary cholesterol
   • Development and practice of wound healing and plastic surgery techniques
   • Study of obesity, anorexia and peptic ulcers and the development of the endoscope
     
     
4. Swine Statistics

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5. Breeds Used for Research:

   Swine used in research can either be domestic pigs produced from agricultural stock or miniature swine, developed specifically for research.

   Domestic swine, such as the Yorkshire, Landrace and Duroc breeds, are large agricultural animals with adult weights of up to 700 or more pounds.  Many farm-purchased pigs are mixed breeds.  These pigs are primarily used in acute studies in which maturity or puberty are not important.

   Miniature swine (minipigs and micropigs) were developed over the past fifty years to provide a conveniently-size pig for experimentation.  These breeds are used in chronic studies that relate to adult metabolism and physiology.  At an adult weight of 100 to 200 pounds, these pigs have organs that are approximately the same size as human structures.  Piglets are bone with a similar degree of maturity and have similar growth patterns to human neonates.  

   Several breeds of miniature pigs are available for use in research.  The Yucatan (Mexican hairless) pig is the only naturally occurring miniature pig.  It is native to Central America and formed the foundation of several breeds of minipigs.  The first miniature pig to be developed what the Hormel pig in 1949.  The Panepinto micropig was developed by Linda Panepinto from Yucatan minipigs in 1978.  These pigs are eighteen inches tall and weigh less than 100 pounds.  The Goettingen miniature pig was developed in Germany in 1980 from crossbreeding a Vietnamese pot-bellied pig with a miniature pig.  Vietnamese pot-bellied pigs are not used in research due to their excitable temperament.

VI  Other Animals Used in Research

There are a wide variety of other species of animals used in research, from zebrafish and sea slugs through dogs and cattle.  Animals are selected according to their suitability to the research project planned.  Each species has advantages and disadvantages that must be weighed before they are selected.

The zebrafish (Danio rereio) has recently been adopted as an important model for the study of vertebrate development and genetics. 

Xenopus laevis, the African clawed frog, is also used to study vertebrate development, especially the early development of the embryo.  They are relatively hardy and easily maintained in the lab.  It was instrumental in the development of the first human pregnancy tests in the 1950s when it was discovered that the injection of urine from a pregnant woman causes spawning (reproduction). 

Poultry are used for a variety of purposes, including embryonic development, antibody production and studies of cardiac disease and surgery.

Armadillos are susceptible to leprosy, a debilitating human disease, and have been an important model in the development of treatments and vaccine.

Marine sponges have been used to study the immune response and its role in autoimmune diseases in which the body turns against itself, such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosis.

Leeches have recently been re-introduced in human medicine as a method to increase blood flow to severed body parts that have been reattached by microsurgery.  Typically, congestion of blood in the reattached part has caused damage by crushing cells.  Leeches drain some of this excess blood, allowing natural healing to occur.

Dogs and cats have been used extensively in research, contributing to the health and well-being of humans and animals.  Cats and dogs each represent less than 1% of all animals used in research annually.  The government regulations pertaining to the care and use of dogs and cats are very strict and detailed.  Legislation protects pets from possible use as research animals.  FIV (feline immunosuppressive virus) although not infectious to humans, is a retrovirus like HIV and has provided a model for studying HIV.  Cats have lead to understanding of the chemical and mechanical aspects of the transmission of nerve impulses.  Pediatric surgical and anesthetic techniques are developed Dogs have been used to advance techniques in cardiac procedures, such as coronary bypass surgery, artificial heart valve replacement and implantation of pacemakers.  The heart-lung machine was created using dogs.  Many other protocols utilize dogs, including teaching. 

Traditional farm animals, other than swine, are also used in research, including horses, sheep, goats and cattle.  When these animals are used in research, they are managed differently than agricultural animals, with specific APHIS regulations.  Transgenic farm animals have been developed.   "Pharming" of drugs, such as growth hormone or insulin, in the milk of a lactating cow or goat is being developed.   Many farm animals are purchased from agricultural production facilities, rather than the licensed dealers that must be used when purchasing dogs, primates and other nonagricultural animals.

Sheep and goats are ruminants used for a variety of research projects including studies of muscular dystrophy, pregnancy toxemia, struvite bladder stones and antibody formation. Sheep are susceptible to a virus-like infection called scrapie that is caused by a prion, the same type of organism that causes bovine spongiform encephalopathy (mad cow disease).  Of special concern when using these small ruminants is Q fever, a zoonotic bacterial disease that is most prevalent in pregnant and lactating animals and that usually cause flu-like symptoms in people  More severe infections may result in persistent disease the requires hospitalization and may be fatal.  California classes sheep as a class 3 biohazard, based on Q fever.   Cattle are also susceptible to Q fever, as well as tuberculosis and brucellosis, two other potentially zoonotic diseases.