Contributions Made by the Colony Dogs to Wheaten Health Completed Grant No

Contributions Made by the Colony Dogs to Wheaten Health

Completed Grant No. 1285: Mode of Inheritance and method for Early Detection of Protein-Losing Enteropathy (PLE) and Protein-Losing Nephropathy in Soft Coated Wheaten Terriers Shelly L. Vaden, PhD; North Carolina State University
Sponsor: Soft-Coated Wheaten Terrier Club of America
Abstract: This study suggests that there are two tests that may be very helpful in early detection of protein-losing enteropathy and/or protein-losing nephropathy -serious diseases in which protein is lost through the intestine or kidneys-in Soft-Coated Wheaten Terriers. These tests, both non-invasive, measure the albumin levels in the urine and the alpha1-protease inhibitor in the feces. The syndrome of protein-losing enteropathy and/or protein-losing nephropathy seems to be increasing and does not manifest itself until the dog is four to six years old, after an affected dog might already have been bred. This study sought to determine how the disease is inherited and to develop an early-detection method. The researchers established a breeding program, involving affected and unaffected dogs. The dogs have been screened for signs of the disease using a variety of methods. As the dogs age, the screening methods can be evaluated in future studies and the mode of inheritance can be determined.

Completed Grant No. 1858: Identifying the Genetic Causes of Renal Dysplasia in Shih Tzu, Lhasa Apso and Soft Coated Wheaten Terriers George Brewer, MD; University of Michigan
Sponsors: American Lhasa Apso Club, American Shih Tzu Club, Soft Coated Wheaten Terrier Club of America
Abstract: This research has narrowed the search for the gene for renal dysplasia to two genes in a region of the genome that has caused kidney disease similar to juvenile renal disease (JRD) in humans. JRD, a genetic disease in which the kidneys fail to develop normally, is thought to occur in 31 breeds. It is seen in high frequency in Shih Tzu, Lhasa Apso and Soft Coated Wheaten Terrier. This project sought to find the mutation or mutations causing JRD in each of these three breeds, using DNA sequences of two candidate genes. Researchers identified the two genes in the region that have caused kidney disease similar to JRD in humans. They plan to sequence these genes and search further for the causative mutation.

Completed Grant No. 1873: Sequential Clinical Evaluation, Mode of Inheritance, and Therapeutic Trial of Protein-Losing Enteropathy and Nephropathy in Soft Coated Wheaten Terriers Shelly L. Vaden, DVM, PhD, DACVIM; North Carolina State University
Sponsor: Soft Coated Wheaten Terrier Club of America
Abstract: Soft Coated Wheaten Terriers (SCWT) are at risk for protein wasting diseases of the kidneys and intestines. Clinical Signs of this disease vary but can be quite severe, including death. We have demonstrated that the disease is associated with food allergies. We propose to continue the evaluation of a colony of SCWT and SCWT-cross dogs that are at risk for the development of this disorder. In face, some of these dogs already have the disease. Sequential evaluation of these dogs will allow us to characterize the early clinical signs, progressive nature, and mode of inheritance of this disease. These findings will allow for future development of a genetic marker as well as selective breeding programs aimed at elimination of this disorder from the SCWT population. Once dogs become overtly affected with this disease, we will enter them into a treatment trial, using methods known to be effective in food allergies. Information obtained from this trial will be invaluable in developing treatment regimens for affected SCWT in the population at large. Results of this study also have applicability to other breeds of dogs that are at risk for food allergies or specific forms of gastrointestinal and renal disease.

Active Grant No. 2219: Longitudinal Clinical Study, Mode of Inheritance, and Therapeutic Trial of Protein-Losing Enteropathy and Nephropathy in Soft Coated Wheaten Terriers Shelly Vaden, DVM, PhD; North Carolina State University
Sponsor: Soft Coated Wheaten Terrier Endowment Fund
Abstract: Soft Coated Wheaten Terriers (SCWT) are at risk for protein wasting diseases of the kidneys and intestines. Clinical signs vary but can be severe, even fatal. We demonstrated that the disease is associated with food allergies. We propose to continue the evaluation of our colony of dogs that are genetically predisposed to this disorder. Some of these SCWT already have the disease. Longitudinal evaluation of these dogs will allow us to characterize the early clinical signs, progressive nature, and mode of inheritance of this disease. These findings will allow for future development of a genetic marker and selective breeding programs aimed at elimination of this disorder from the SCWT population. Once dogs become overtly affected with this disease, we will enter them into a treatment trial, using methods known to be effective in food allergies. Information obtained from this trial will be invaluable in developing treatment regimens for affected SCWT in the general population. The youngest dogs in our colony have been weaned directly to a unique diet to determine if diet can be used to prevent disease. Results from these studies have applicability to other breeds of dogs that are at risk for food allergies and/or specific gastrointestinal and renal diseases.

Active Grant No. 2279: Longitudinal Field Studies of Families of Soft Coated Wheaten Terriers Affected with Protein-Losing Enteropathy and/or Protein-Losing Nephropathy and the Foundation of a DNA Bank Meryl Littman, VMD, DACVIM; University of Pennsylvania
Sponsor: Soft Coated Wheaten Terrier Club of America
Abstract: An inherited predisposition for diseases causing protein loss from the intestine (protein-losing enteropathy, PLE) and kidney (protein-losing nephropathy, PLN) has been found in Soft Coated Wheaten Terriers. Dogs often show no signs of illness until middle age, and by then many dogs have been bred. Tissue biopsies commonly show inflammatory bowel disease and immune-mediated glomerulonephritis. The mode of inheritance is not proven, and an environmental trigger may be necessary for expression. After diagnosis, most dogs succumb to their disease within a year despite therapy, and some die suddenly. Currently there is no predictive test to determine which animals may later become ill (affected), which may be passing on at-risk genes (carriers), and which animals are normal. By studying families of affected dogs and monitoring individuals annually with screening tests to detect early signs of abnormalities, we will study the significance of those changes, the clinical course of these diseases and we will attempt to alter the course with diet changes and medications. We will be able to store and begin to study DNA from affected animals, their families, and geriatric healthy animals, in an effort to find a genetic test to help identify affected, at-risk, and normal individuals.

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Created 12/24/04