PARTNERS IN SEEKING SOLUTIONS: UC DAVIS RESEARCHERS AND CAT BREEDERS WORK TOGETHER AGAINST FELINE DISEASE

The quest for solutions to companion animal disease can be a long and complex journey. To achieve success, veterinary researchers must use a wide variety of techniques and skills that include clinical work, laboratory experimentation and analysis, evaluation of related research, fundraising and grant writing, and above all, patience and persistence. Another key component is collaboration, which often involves academic colleagues.

 

But researchers at the UC Davis Center for Companion Animal Health and the Koret Center for Veterinary Genetics of the Veterinary Genetics Laboratory also work closely with community practice veterinarians, animal shelters, rescue groups, pet owners, and breeders to find ways to identify, treat, and prevent disease.

In feline veterinary medicine, diseases generally do not differentiate between random-bred and pedigreed cats. And while medical advances benefit cats regardless of heritage, pedigreed cats offer a distinct advantage to genetics researchers.

To understand diseases that are caused or affected by genetic traits, researchers must be able to study multiple generations of related animals. This is more difficult with random-bred cats of unknown ancestry.Fortunately, breeders of pedigreed cats register animals with organizations such as the Cat Fanciers Association or The International Cat Association, establishing pedigrees that can span decades. Many also track and document health histories for cats and their recent ancestors, which is invaluable for research into heritable diseases. At the CCAH, collaborations between researchers and cat breeders have already produced important breakthroughs in feline medicine.

Polycystic Kidney Disease: A Veterinary Genetics Laboratory Success Story

Persian cats and breeds created from them, including Himalayans, Exotics and British Shorthairs, are known to be susceptible to polycystic kidney disease (PKD), a genetic disorder. It is characterized by the growth of fluid-filled cysts that produce significant deformation and scarring of the kidneys and can damage other organs in the body. In cats the disease manifests at about age 7, leading to a decline in kidney function and ultimately to end-stage renal failure. The signs of PKD include weight loss, lethargy, vomiting, excessive thirst and frequent urination.

PKD research began in the late 1980s, when as many as one-third of all Persian cats were believed to be carriers. By the mid-1990s, research had demonstrated that the gene was not linked to a cat's sex, but if a carrier were bred to a noncarrier, 50 percent of the offspring would be carriers. During that period the only way to test for PKD was through ultrasound imaging, which would only reliably reveal the disease after it was well established. Genetic testing was not yet available for cats.

Then in 1999, as the field of genetic research was rapidly expanding into both human and animal medicine, Leslie A. Lyons joined the UC Davis faculty. One of the first projects Dr. Lyons undertook was to determine if a genetic marker could be found for PKD. Dr. Lyons put out a call to Persian breeders to bring cats to Davis for free PKD ultrasound clinics. Breeders from around the country responded to her request, bringing cats and pedigrees of breeding lines they knew had been affected by PKD as well as those of non-affected lines. Ultrasounds were performed and blood samples were collected. After the clinics, Dr. Lyons' team built an extensive database of pedigrees and DNA samples for large families of affected and nonaffected cats. Samples from the two groups were carefully analyzed and compared, and in 2002 Dr. Lyons and her team succeeded in identifying a genetic marker for carriers of PKD. Shortly thereafter the VGL hosted another clinic, this time offering genetic testing to identify PKD carriers along with ultrasounds to evaluate disease progression. Papers on this landmark study were published in 2004.

Thanks to the genetic test that Dr. Lyons and her team developed, with the help of breeders, PKD carriers are gradually being eliminated from Persian and related-breed gene pools around the world. It is also important to note that because PKD in Persian cats resembles autosomal dominant polycystic kidney disease in humans, this study serves as a valuable model for human research.

Meeting the Challenge of Feline Infectious Peritonitis

Probably the most dreaded feline disease that cat lovers face is feline infectious peritonitis (FIP). FIP can affect as many as one in 20 cats coming from shelters, rescue groups and catteries, and it has the highest mortality rate of all feline infectious diseases--it is virtually 100 percent fatal. There is no effective treatment, nor is there a simple and reliable definitive test for the disease. FIP is especially heartbreaking because it primarily affects kittens and young adults from 4 months to 3 years of age, at the beginning of their relationships with their human families. And FIP can strike suddenly and without warning weeks, months and even years after initial infection.

FIP is caused by a mutation of the feline coronavirus. Coronaviruses of various types exist in animals and humans, usually causing nonfatal respiratory or intestinal disease. An exception was the severe acute respiratory syndrome (SARS) epidemic in 2002-2003, which occurred when a form of the coronavirus in an Asian civet mutated and jumped to humans. Fortunately, the outbreak was short lived, as the virus was never able to fully adapt to humans and to be readily transmitted from person to person.

The feline coronavirus is ubiquitous, an estimated 70 to 80 percent of all cats have been exposed. After infection, some may show signs of mild intestinal disease, while others show no signs at all. Cats can also become carriers of the virus, which replicates in their digestive system and is shed in their feces, continuing the cycle of exposure. Mutations of the feline coronavirus seem to occur frequently, though most have very little impact on infected cats. However, when the virus mutates into FIP it has devastating effects on a cat's immune system. The most common form, known as "wet" FIP, causes inflammation of the abdominal cavity, resulting in significant accumulation of fluid in the belly. FIP can also take a more chronic "dry" form, which produces masses in the kidneys and other organs, and in the central nervous system. This can affect the eyes, making them look cloudy, and also can cause progressive neurologic abnormalities.

Other signs of FIP include lack of appetite, weight loss, stunted growth, persistent high fever, depression, rough coat, and increased susceptibility to secondary infections such as respiratory disease. Unfortunately, many of these signs are also symptomatic of other diseases. Because there is no simple and reliable definitive test for FIP, cat lovers can spend a great deal of time and money on diagnostic tests and anecdotal treatments, only to lose their beloved cat.

Hundreds of FIP studies have been conducted since the disease was first clinically diagnosed in 1963. Though no practical solutions have yet been found, researchers continue to gain a better understanding of FIP thanks in part to cat breeders who observed that some bloodlines were more susceptible to FIP and that certain matings would inevitably produce kittens that would succumb to FIP later in life.

With UC Davis, Persian breeders again played a role in research by helping to understand FIP's heritability. Researchers recommended that Persian breeders neuter males that produced FIP kittens, because males could produce so many more kittens and thus had a greater genetic influence. Over time, this resulted in reducing the occurrence of FIP in their breed and reinforced the evidence that genetics likely plays at least a 50-percent role in how a cat's immune system responds to the coronavirus.

To further study genetic susceptibility to FIP, UC Davis researchers once again are working with breeders, and are acquiring pedigrees and DNA samples for breed-specific studies involving Birmans, Burmese, Bengals, Persians, Ragdolls and other cat breeds. While FIP is not known to affect one breed more than another, specific breeds have been selected that are inbred to a degree and have seen a recent rise in FIP deaths.

For this study the CCAH is gathering samples from three groups: cats dying of FIP, cats related to those affected by FIP, and cats that come from lines with no history of the disease.

 

New Hope for the Future of Feline Disease Research

New technology and recent advances in feline medical research provide hope for the future, not only for for feline infectious peritonitis but also for many other feline diseases. Sequencing of the feline genome is nearly complete, and is a significant step forward that will provide researchers with a new set of tools to answer essential questions about feline disease. Dr. Niels Pedersen, director of the CCAH and a world authority on feline infectious diseases, along with Dr. Leslie Lyons and other FIP researchers at UC Davis, hopes to discover the gene or genes involved in FIP susceptibility and resistance, and to develop tests to identify cats that carry these traits as they did for PKD in Persians. Information collected from breeders will play a key role in developing an FIP genetic test.

Thanks to major advances in medical technology during the last decade, Dr. Pedersen and his team at UC Davis are able to examine viruses at the molecular level and extract and sequence entire virus genomes. This allows them to study how viruses and host cells interact, which is important for antiviral drug development. They are also working with local animal shelters, through the UC Davis Koret Shelter Medicine Program, to help reduce the incidence of FIP and to study the transmission and progression of the disease in random-bred cats.

A global consortium known as SOCK FIP has recently been formed to focus on FIP research at UC Davis. This will allow UC Davis researchers to do their part in the worldwide effort to better understand, prevent and even cure this terrible disease. Armed with new tools and techniques, and the insights and understanding achieved after decades of research, there is every reason to hope that these scientists will be able to make breakthroughs in FIP disease identification and management.

Cat Lovers Who Want to "Sock It" to FIP

The quest for solutions to FIP has been a long journey, and will continue. Unfortunately, so will the heartbreak of losing cats to the disease until answers can be found. And finding those solutions can be expensive.

In the 1970s, volunteers formed a group called Save Our Cats and Kittens (SOCK) to help raise funds to support feline leukemia research at UC Davis. In the 1960s and 1970s, feline leukemia was the leading cause of death of as many as one-third of sick cats.

Thanks to the fundraising work of SOCK members, and the skilled researchers at UC Davis, rapid diagnostic tests and vaccines were developed that ultimately reduced feline leukemia to an infection of limited importance. In 2008, SOCK was revived. Now a new group of volunteers is working to support FIP research at UC Davis. The group's mission also includes helping cat lovers everywhere to gain a better awareness and understanding of the disease.

Funding is needed to carry out research on tests and treatments for FIP, for example, to purchase DNA chips that are vital not only to FIP research but also to genetic studies that can unlock doors to understanding and curing many feline diseases.

SOCK FIP volunteers include cat lovers, rescue groups, breeders, veterinarians, researchers and shelter workers. All have known the heartbreak of the disease, and all want to find ways to SOCK it to FIP.

 

For more information on SOCK FIP visit the website, www.sockfip.org.

This article was originally published in the the UC Davis School of Veterinary Medicine Center for Companion Animal Health Fall 2009 Newsletter.

Nancy L. Reeves is a development writer at Stanford University. She is also a Burmese Cat Breeder, newsletter editor for the United Burmese Cat Fanciers, member of the Cat Writer's Association, Burmese breed liaison for the FIP genetics study, and a volunteer for SOCK FIP.