Yorkshire Vol. 4, No. 1 ■ December 2011

Researchers Seek Candidate Genes for Protein-Losing Enteropathy

esearchers at Cornell University developing lymphangiectasia than can be developed that would identify School of Veterinary Medicine in other breeds. affected and thus provide a diag - RIthaca, N.Y., are working to find Recognizing the widespread nostic tool for the disease. Currently, candidate genes that predispose York - occurrence of PLE in the breed, the the only definitive test to detect and shire to protein-losing enteropa - Yorkshire Terrier Club of America and distinguish between different causes thy (PLE), a potentially fatal condition the Yorkshire Terrier Club of America of PLE is an intestinal biopsy that is in which dogs lose significant protein Foundation recently helped fund an expensive, requires general anesthesia into their gastrointestinal system. AKC Canine Health Foundation grant and carries some health risks. While genetics are likely to play a that supports the Cornell University The severity of PLE varies among role in determining which dogs are research. The researchers’ ongoing individual dogs and may be related predisposed to developing PLE, envi - efforts to collect DNA samples from to differences in genetic expression ronmental factors, such as enteric affected and normal dogs are instru - of the disease. Some dogs show no (intestinal) bacteria or food intolerance mental to the success of the study. clinical signs, yet die quickly. Others or allergy, may contribute as well. “Our goal is to identify a gene change exhibit serious manifestations, but The extent to which environmental or set of changes that predispose a with proper disease management do factors influence the disease is not to PLE,” says lead investigator well. , anorexia, , fully known. Nate Sutter, Ph.D., assistant professor lethargy, weight loss, edema (swelling) In Yorkshire Terriers, PLE is widely of medical genetics. “The evidence or ascites (fluid in the abdominal attributed to lymphangiectasia, a that PLE has a genetic component cavity), and respiratory difficulty condition in which the lymph vessels primarily rests on the observation that from fluid in the chest are not become dilated and disrupt the normal some breeds — such as Yorkies — are uncommon signs in dogs with PLE. flow of lymph throughout the body. at an elevated risk for the disease. The Other at-risk breeds for PLE are Recent studies have showed extensive simplest explanation is that at-risk Basenji, Chinese Shar-Pei, Norwegian cystic dilatation of the intestinal crypts breeds have one or more genetic Lundehund and Soft-Coated Wheaten (mucosal glands of the epithelial lining factors that confer risk.” Terrier. The genetic basis for the dis - of the small intestine) also may con - Ultimately, once a genetic marker ease may vary by breed. Besides lym - tribute to PLE. One study showed that is identified and the causative muta - phangiectasia, conditions that can Yorkies have a tenfold greater risk of tion for PLE is discovered, a DNA test Continued on page 2

Managing a Lifelong Condition the specialist recommended an intestinal biopsy to determine definitively whether Winnie had PLE. rotein-losing enteropathy associated with lymphan g- Only weeks after the first signs of PLE, Winnie died Piectasia and crypt cysts is a fatal condition in as many of peritonitis following the intestinal biopsy procedure. as half or more Yorkshire Terriers, experts estimate. Most “It was probably a result of the disease causing changes diagnosed dogs receive lifelong therapy. Some dogs never that weakened the intestinal walls,” Fallon says. improve despite therapy, while others continue to live a “Chloe,” a 12-year-old Yorkshire Terrier owned by Jane normal, active life. Here are stories of the journeys of Downey of Columbus, Ohio, continues to thrive despite owners whose Yorkshire Terriers were diagnosed with PLE. having been diagnosed with PLE when she was 9 years Liz Youngblood of Seattle was pleased when her 7 1/2- old. “I have to work hard to keep Chloe’s weight down year-old Yorkie, “Taffy,” responded well to medications given with a strict diet,” Downey says. “She loves to get into to help reduce the signs of PLE. “In the beginning, Taffy the other dogs’ food bowls, so it’s a constant struggle. was well enough to play and enjoy herself,” she says. If she overeats, she gets bloated.” Not long afterward, diarrhea and fluid on the abdomen Another long-lived Yorkshire Terrier diagnosed with returned. “Then, Taffy began struggling to breathe,” says PLE is “Martha,” a retired conformation champion belong - Youngblood. “We had the fluid drained off several times, ing to Stephanie Ruiz of Orange County, Calif. Martha but it always came back.” was diagnosed at age 9 and today is 15. “When we The fluid-draining procedure was painful and put Taffy were still working on a diagnosis, we tried several diets at risk for peritonitis, or inflammation of the membranes for Martha, but none seemed to help,” Ruiz says. lining the abdomen. After seven months, Youngblood Once Martha was definitively diagnosed with PLE, the made the difficult decision to have Taffy euthanized. prescribed medications to help manage signs Pancreatitis was the initial diagnosis given Denise of the disease. “The key for us is consistently following Fallon’s Yorkie, “Winnie,” who had lost her appetite and the veterinarian’s instructions regarding diet and medi ca - frequently vomited. After two weeks on a bland diet, tions,” says Ruiz. “Martha’s protein level is normal, and she Winnie continued to weaken. Fallon, of Mechanicsburg, has lived longer than any Yorkie we have ever owned.” Pa., was referred to a veterinary teaching hospital, where Researchers Seek Candidate Genes first, she didn’t eat well, even with an autosomal recessive or dominant continued from page 1 the prednisone. We could see she was inheritance pattern. wasting away and was losing muscle “Many Yorkshire Terriers with PLE lead to PLE are inflammatory bowel mass. We could see the bones in her succumb to the disease despite disease, intestinal lymphoma and fungal shoulders and feel her spine. We were aggressive therapeutic intervention,” infections such as histoplasmosis. so afraid we would lose her.” Simpson says. “The reasons for a good Dogs with PLE lose protein from the After a couple of weeks, the veteri - response versus a poor response are body through the intestines. Normally narian increased Phoebe’s prednisone. not clear.” the intestines absorb dietary protein “It was like magic,” says Fritz-Rubert. In the future, once sufficient num - from food during the digestive process, “Within five days, Phoebe went from bers of samples are collected, the team but the reverse happens in dogs with weighing 7 pounds to 5 pounds, and plans a genomewide association scan - PLE. In these dogs, the protein is she lost 4 inches around her belly. The ning that will help them to identify released into the intestines and lost weight loss was because her ascites regions of genes that vary among in feces. improved.” affected and healthy Yorkies. “This Several months after Phoebe was genetic assay provides genotypes Signs of a Similar Condition diagnosed with PLE, good news came from roughly 170,000 SNP (single Chronic occasional vomiting was nucleotide polymorphism) markers,” common in Julie Fritz-Rubert’s 4 ½- Sutter explains. “These markers occur year-old Yorkshire Terrier, “Phoebe.” How to Contribute to PLE all over the dog genome and give us When the dog vomited six times in Genetic Research a nice survey picture of an individual one day, she became concerned. A dog’s genome. few days later, the dog’s abdomen reeders and owners of Yorkshire “Each SNP marker on the chip has appeared bloated. “I took Phoebe to BTerriers can contribute DNA two allele forms. If we find a SNP the veterinarian, who suspected she samples to help advance genetic marker allele, or form, in affected had gastroenteritis but ran blood research at Cornell University School dogs that is not present in healthy work to be sure,” says Fritz-Rubert of Veterinary Medicine to identify dogs, we could have a correlation of Sacramento, Calif. candidate genes that cause protein- between the genotype and the dis - The blood test showed that Phoebe losing enteropathy (PLE). The ease phenotype. Since we know the had low levels of albumin and globulin, researchers are requesting samples genomic location for each SNP, we consistent with PLE. The veterinarian from affected dogs of all ages and could then look at the location, or recommended an intestinal biopsy to from older, healthy dogs. locus, in the genome for clues about determine definitively whether Phoebe For information about the criteria the disease.” had lymphangiectasia or another cause to qualify and how to submit samples Next, the researchers will zero in of PLE. The biopsy confirmed that Phoebe and pedigree and clinical informa - on that locus to make a finer grained had mild to moderate lymphangiectasia. tion, please contact Dr. Kenneth map showing differences and to help The lymph vessels in Phoebe’s body Simpson at [email protected] or identify the location more precisely. were dilated due to pressure from 607-253-3567, or Dr. Nate Sutter “Only after that step is completed inflammation. The lymph vessels in at [email protected]. will we be in a position to create a the intestines, called lacteals, were DNA test to help breeders gauge the not able to absorb dietary fat because risk for disease,” Sutter says. of increased intralymphatic pressure on a veterinary visit. “It turned out As the research continues, the goal with subsequent malabsorption of Phoebe had gained too much weight,” is to collect 100 samples of DNA from fat and other nutrients such as fat Fritz-Rubert says. “Her big belly was affected dogs and healthy controls. soluble vitamins. With the loss of due to fat, not fluid as we had feared.” “We need to collect DNA samples, nutrients, particularly protein and fat, Not only had Phoebe gained weight, pedigrees and clinical data from Phoebe had begun to lose weight. but her albumin and globulin levels Yorkies with and without disease,” Disease management focused on were normal. The regained says Sutter. reducing inflammation in the intestinal muscle mass and began feeling good, Phoebe’s DNA will be included in mucosa and fluid accumulation in the even playing. Phoebe continues to take the study. Fritz-Rubert became an abdomen. A corticosteroid, prednisone, a small dose of prednisone and is fed advocate for supporting the genetic was prescribed for the inflammation, a low-fat diet and low-fat treats. She research while learning about the and an immunosuppressive medication, also continues to take the immuno - disease through Phoebe. “I probably azathiaprine, was given to control suppressive medication, azathioprine, have spent about $4,000 in medica - overaggressive immune responses. which clearly states on the label: Give tions and veterinary visits for Phoebe,” Dogs diagnosed with PLE may be medicine every other day, forever. she says. “The emotional toll has given medications such as tylosin or been just as costly.” metronidazole, which also help to Surveying the Dog’s Genome When she found an online forum modulate bacteria that may promote Once a dog is diagnosed with (http://www.savelouie.com/ phpBB3/ ) inflammation and reduce the risk of protein-losing enteropathy, the con - for people whose dogs suffer from bacteria being transferred into the dition usually requires lifelong disease PLE, Fritz-Rubert welcomed the com - body through the impaired gut. Low- management. The ability to recognize fort of sharing her experiences with dose aspirin helps to reduce the risk affected dogs sooner and begin pre - others. “I discovered this while of thromboembolism, a blood-clotting ventive care sooner may offer a better Phoebe was in the hospital,” she says. disorder that is common in dogs with prognosis. Should a DNA test one day “I have learned so much from reading PLE, and a low-dose diuretic may be become available to determine dogs other people’s stories. We have lost lots given to reduce intra-abdominal fluid. that carry the PLE-associated gene of dogs to this, and each one breaks often recommend mutation, breeders will have a tool to my heart.” ■ feeding a low-fat diet enriched with potentially reduce disease incidence medium-chain triglycerides rather than in their litters. the long-chain triglycerides found in Sutter, the Cornell University Purina appreciates the support most dietary fat. The shorter chain researcher leading the genetics study of the Yorkshire Terrier Club of triglycerides may be absorbed directly of PLE in Yorkshire Terriers, is working America and particularly Mary into the bloodstream, bypassing the with Kenneth Simpson, professor of Trimble, president of the YTCA lymph system. small animal medicine who specializes Foundation, in helping to identify Even with medications and a special in gastroenterology. Though their initial topics for the Purina Pro Club diet, Phoebe’s abdomen was enlarged grant was completed last May, the Yorkshire Terrier Update newsletter. for about six weeks. “We could tell she research still is in the early stages, didn’t feel well,” Fritz-Rubert says. “At with no indication whether PLE has

2 Purina Pro Plan Takes Main Stage at National Pheasant Fest & Quail Classic

ips from top professional train - Sporting Dog Group, will emcee panel and bird dog enthusiasts, the event ers of retrieving, flushing and discussions in which the trainers will will feature wildlife conservation, Tpointing breeds are among the answer questions from attendees. upland game bird hunting and wildlife featured activities planned at the habitat management and restoration. National Pheasant Fest & Quail Classic About 30 sporting dog breeds are Feb. 17 to 19 at the Kansas City (Mo.) expected to be represented by breed Convention Center. Purina Pro Plan is clubs and trainers on Bird Dog Alley. the national dog food sponsor of the Purina and Pro Plan was named in annual event that draws more than early 2011 as the national dog food 20,000 people. sponsor of Pheasants Forever and The professional trainers, who are Quail Forever, the largest nonprofit Purina consultants, will hold seminars organization in the country dedicated on the Main Stage of the Bird Dog to upland habitat conservation and Bonanza area. Tom Dokken of Dokken’s “We are excited to invite our Purina one in which seven of 10 members Oak Ridge Kennels in Northfield, Minn., consultants to this event and to share own dogs. The agreement renewed will offer retriever training tips. Rick their expertise on conditioning and Purina’s more than two decades’ Smith of Cozier, Va., who developed training dogs,” West says. “At the support of Pheasants Forever, which the Silent Command System of dog Purina booth, we will have experts was founded in 1982 by avid pheasant training, and his cousin, Ronnie Smith, on hand to discuss nutrition and care hunters and conservations. Quail will present guidelines on training for hardworking dogs.” Forever was launched in 2005. ■ pointing and flushing breeds. The largest trade show in the Bob West, Director of Purina’s country for pheasant and quail hunters

2011 Pro Plan Champions Cup Standings Dog Breed/Variety Points Earned* GCH Casablanca’s Thrilling Seduction Black Cocker Spaniel 315 GCH Palacegarden Malachy 228 GCH Saks Hamelot Little Drummer Boy Frise 174 GCH Cragsmoor Buddy Goodman 171 GCH Winfall Brookwood Styled Dream Boxer 167 GCH Banana Joe Van Tani Kazari 166 GCH Starline’s Chanel 151 GCH Northgates As You Like It Pharaoh 140 GCH Babheim’s Captain Crunch German Shepherd Dog 132 GCH Szumeria’s Wildwood Silver Six Pence Kuvasz 117

*Points earned through November 30, 2011.

Purina-Sponsored Sporting Events January to March 2011* Event Date Location United Kennel Club (UKC) Grand American Jan. 6 - 7 Orangeburg, SC U.S. Complete Shooting Dog Association (USCSDA) Jan. 12 - 15 Cheraw, SC National Open Championship Continental Championships Jan. 16 - 28 Greenville, FL National Bird Hunters Association (NBHA) Jan. 20 - 23 Oneonta, AL Invitational Championship UKC Winter Classic and Purina Coonhound Awards Jan. 27 - 28 Albany, GA All-American Foxhound Championship Feb. 3 - 5 Grenada, MS NBHA National Amateur Championship Feb. 10 - 12 Wheatstone, MO National Championship Feb. 13 - 26 Grand Junction, TN National Pheasant Fest & Quail Classic Feb. 17 - 19 Kansas City, MO UKC Southeastern Treeing Walker Days Feb. 23 - 25 Salisbury, NC National German Shorthaired Association (NGSPA) Feb. 24 - Mar. 4 Booneville, AR National Championship NBHA National Open Feb. 29 - Mar. 4 Cheraw, SC USCSDA Futurity Mar. 7 - 8 Sandland Wildlife, West End, NC Brace Southern Federation Mar. 9 - 14 Rock Springs, GA American Hunting Basset Association (AHBA) World Hunt Mar. 16 - 17 Lynville, IN Mid-America Brace Gundog Federation (MAB) All-Age Mar. 24 - 25 Booneville, IN National Run-Off NBHA Futurity Mar. 26 - 29 Nashville, TN

*This table lists some, but not all, upcoming sporting events sponsored by Purina.

3 Purina Pro Plan Sponsors the 2012 Westminster Kennel Club Dog Show

ew in 2012 at the Westminster ners, including the last five Best in Kennel Club Dog Show, dog show winners, have been fed Purina Nhandlers and enthusiasts arriving Pro Plan brand dog food, so it’s for the 136th annual show will notice fitting for Purina to partner with signature purple Purina Pro Plan this distinguished kennel club.” banners decorating Madison Square A longtime supporter of the Garden in New York City. dog fancy, Purina sponsors more As the official pet food sponsor of than 100 all-breed and specialty dog the prestigious dog show, Pro Plan shows a year. In 2010, Purina will reach out to the dog fancy and unveiled the Purina Event Center, a was selected due to its stature in the millions of people watching the tele- $15 million, 84,000-square-foot pet industry and visibility at dog shows,” vised program live on USA Network. indoor dog show facility in Gray says David Frei, Director of Communi - Purina and the Westminster Kennel Summit, Mo., where six Westminster cations for Westminster. “Purina will Club announced the multi-year Best in Show winners, along with be a very active partner, not just during sponsorship agreement last June. their owners and handlers, participat- the dog show but year-round.” “Westminster is a marquee dog ed in the Grand Opening. Founded in 1877, the Westminster show well known around the world,” Purina’s support of the fancy con- Kennel Club Dog Show is the oldest says Candy Caciolo, Purina Portfolio tributed to the decision by the West- organization in the country dedicated Director of Specialty, Breeder and Pet minster Kennel Club to choose Purina to the sport of purebred dogs. The 2012 Acquisition. “Many Westminster win- as the sponsor of its dog show. “Purina dog show will be held Feb. 13 and 14. ■

Purina-Sponsored Dog Shows January to March 2012* Event Date Location Kennel Club of Palm Springs Dog Show Jan. 5 - 8 Indio, CA Land O’Lakes Cluster Jan. 6 - 8 St. Paul, MN Florida Classic Cluster I & II Jan. 12 - 22 Brooksville, FL Orange Empire Kennel Club Dog Show Jan. 27 - 30 San Bernardino, CA Cherokee Rose Cluster Feb. 2 - 5 Atlanta, GA Westminster Kennel Club Dog Show Feb. 13 - 14 New York City, NY Foothills Dog Show Circuit Feb. 17 - 19 Spartanburg, SC Rocky Mountain Cluster Feb. 17 - 20 Denver, CO International Kennel Club (IKC) of Chicago Dog Show Feb. 23 - 26 Chicago, IL Fiesta Cluster Mar. 2 - 5 Scottsdale, AZ Belle City Cluster Mar. 3 - 4 Purina Event Center Purina Farms Gray Summit, MO March Madness Cluster Mar. 22 - 25 Edison, NJ Fort Worth Cluster Mar. 23 - 25 Fort Worth, TX

*This table lists some, but not all, upcoming sporting events sponsored by Purina.

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