American German Shepherd Dog Charitable Foundation News
American German Shepherd Dog Charitable Foundation, Inc.
1401 South River Oaks Drive, Mahomet, IL 61853
Reports received April 15, 2007
Cornell University
Active Grant No: 276: Microarray Analysis for Cardiac Gene Expression in German Shepherd Dogs with Sudden Death
Disease(s): Heart Disease
Sponsor(s): American German Shepherd Dog Charitable Foundation, German Shepherd Dog Club of America
Researcher(s): N. Sydney Moise, DVM, MS
Breed(s): German Shepherd Dog
Abstract: Sudden death in dogs due to cardiac disease is common. Many of these dogs die because of abnormal beats of the heart. Such diseases are likely inherited in the dog. Breeds at risk for such a cardiac death include the Doberman Pinscher, Boxer, Great Dane, Irish Wolfhound, Afgan Hound, Newfoundland and the German Shepherd Dog (GSD). To discover the genetic mutations that cause the diseases in each of these breeds will take many years of work. Research to identify the means of marking abnormal genes will help us to find the mutations. Even though the mutations will be different, research in one breed will help other breeds as we can use the gained information as we search the canine genome for the fatal inherited mistake. GSD have an inherited propensity for sudden death due to the occurrence of abnormal heart beats that develop primarily during sleep or with certain anesthetic
agents. We have the needed pedigrees from GSD for our research. In this proposal we put forth a comprehensive plan to used stored samples from GSD that have died and their relatives so that we can identify potential abnormal genes and develop the markers for the most likely genes that could be involved in the disorder.
Significant Accomplishments: Markers for many genes now developed. This will hopefully be of use to others studying either this or even unrelated diseases for which these may be candidate genes.
University of Pennsylvania (University)
Active Grant No: 390: Extended Medical Surveillance of Dogs Deployed to the World Trade Center and the Pentagon
Disease(s): Search and Rescue
Sponsor(s): AKC CAR, German Shepherd Dog Club of America, Golden Retriever Foundation
Researcher(s): Cynthia Otto, DVM, PhD
Breed(s): All (non-specified), Golden Retriever
Abstract: We have been monitoring the health and behavior of the search and rescue dogs deployed on 9/11/01 to the World Trade Center and Pentagon disasters since shortly after those events took place. During the first year of surveillance, significant changes were identified in the blood work of the deployed dogs versus the control dogs. These changes proved temporary however, and in year two of the study, blood work values mostly returned to normal. These initial changes suggest that deployed dogs were exposed to more hazardous substances during deployment and ultimately these substances are likely to cause long-term health changes. Additionally, ten deployed dogs and two control dogs have died since surveillance began. This rate of mortality, while not completely unexpected in this size population, is important considering the major cause of death in deployed dogs was cancer. Another
four deployed dogs have been diagnosed and are currently living with cancer. It is essential that we evaluate these dogs throughout their lifespan to determine whether the 9/11 deployment is a factor in the rate and onset of cancer in these dogs.
Significant finding: At this time, no particular cancer is more prevalent in deployed vs control dogs and there was no increase in rate of cancers in dead deceased vs deceased controls.
University of Colorado (University)
Active Grant No: 615B: Heritable and Sporadic Genetic Lesions in Canine Lymphoma Disease(s): Cancer
Researcher(s): Matthew Breen, PhD
Active Grant No: 615A: Heritable and Sporadic Genetic Lesions in Canine Lymphoma
Researcher(s): Jaime Modiano, VMD, PhD
Disease(s): Cancer
Sponsor(s): Akita Club of America, Inc., American Bloodhound Club, American Boxer Charitable Foundation, American Bullmastiff Association, American German Shepherd Dog Charitable Foundation, Atlantic States Briard Club, Inc., Bernese Mountain Dog Club of America, Briard Club of America, Chinese Shar-Pei Charitable Trust, Collie Health Foundation, Doberman Pinscher Club of America, Flat-Coated Retriever Foundation, French Bulldog Club of America, German Shepherd Dog Club of America, Golden Retriever Foundation, Labrador Retriever Club, Orthopedic Foundation for Animals, Portuguese Water Dog Club of America, Inc., Rhodesian Ridgeback Club of the United States, Rottweiler Health Foundation, San Joaquin Kennel Club, Scottish Terrier Club of America Health Trust Fund, St. Bernard Club of America, Starlight Fund, Vizsla Club of America Welfare Foundation
Breed(s): All (non-specified), Boxer, Golden Retriever, Portuguese Water Dog
Abstract: It has been apparent for some time that certain dog breeds are prone to develop certain types of cancer. Specifically, studies completed between the late 1960's and the early 1980's defined relative risk of lymphoma for different dog breeds. Yet, there has been little progress since then to define factors that account for this risk. As part of ongoing programs supported by the AKC CHF in our laboratories, we showed recently that the breed-specific risk of lymphoma extends beyond the simple disease condition to a predisposition for specific forms of lymphoma. More importantly, we showed there are recurrent chromosomal abnormalities that segregate with specific forms of lymphoma and that are more common in Golden Retrievers than in other breeds, suggesting breed-specific profiles of genetic abnormalities will be found in canine lymphoma. To continue this work, we plan to use
contemporary (array-based) technologies to identify genes that map to these regions and how they contribute to the disease. We anticipate that the results from this work will allow us to predict how heritable factors influence the occurrence of abnormalities in these genes, and will set the groundwork to identify specific genes associated with breed-dependent cancer risk.
Performance Summary: Principal Investigator is ahead of schedule and has hybridized samples from dogs with chronic lymphocytic leukemia and analysis of those micro array data has begun. Suitable numbers of dogs with tumors samples have been obtained; excellent progress.
University of Florida
College of Veterinary Medicine
Researcher: Dr. Roger Clemmons
Disease: Degenerative Myelopathy of the German Shepherd Dog (GSDM)
Sponsor: American German Shepherd Dog Charitable Foundation
Report from Dr. Clemmons
This past year has been exciting and productive. We uncovered specific changes in DNA of dogs with GSDM (based upon ante-mortem diagnostics). First, there is a priming error in region DLA-DRB1 associated with a point change in allele*1101, the DM Flash test. This is a new allele*1101J. The location of allele*1101J is where DNA encodes T cell recognition of antigens and predispose for auto-immune diseases. There is a 70 BP deletion in the DNA region that encodes folding of myelin basic protein and is thought to result in increased antigenicity of MBP in Finish MS patients. Most GSDM dogs have changes in 2 regions associated with primary progressive MS, confirming that GSDM is PPMS. The region associated with exacerbating/remitting MS is normal. We have also evaluated new medications. PEG, which is effective in treating acute spinal cord disease, has minimal effectiveness on initial dosing
only. Stem cell therapy with intrathecal (but not intravenous) bone marrow-derived progenitor cells improves motor function and spinal conduction for a short time. Stem cell therapy can be safely done and repeatedly, but may not be the final answer. We are evaluating whether the nerve growth factors that these cells produce are what is needed and whether a more long-term delivery system for these factors can be found. Trials with drugs which help human PPMS patients have begun to see if they will help GSDM patients. So, we are close to understanding what GSDM is and to developing new strategies for its treatment.
The DM Flash Test has allowed for testing of normal and affected dogs and there is a high probability of affected dogs to carry several characteristic loci in their genomes. In this study, we will determine the incidences of GSDM-related genes in a large number of GSDs and evaluate the clinical significance of these findings. In a small pilot study, approximately 20% of GSDs carry the potential to develop GSDM. This study will expand upon these findings and confirm the data rom the smaller sample. We will also attempt to determine if there are geographic congregations of such genetics in this country. This study will help us to identify relative risk of GSDM in the GSD. We hope that the study will allow us to identify individuals at risk so that we can try to modify their potential to develop GSDM in the future.
Degenerative Myelopathy Research-Dr.Roger Clemmons-University of Florida-Grant Results
Report received May 24, 2005:
Dr. Clemmons has, today, completed the first autologous bone marrow-derived stem cell transplant in a dog with German Shepherd DM. Dr. Clemmons and his team are cautiously optimistic that it will help but it is too early to determine that. He will be monitoring this dog over the next month to see if there are improvements in neural function. What we know so far, is that it has not appeared to have any adverse effects in the first 12 hours after transplantation. The dog has shown no fever, is happy and hungry.
Degenerative Myelopathy Research-Dr.Roger Clemmons-University of Florida-Grant Results
Report received December 4, 2004:
We are now able to accept samples for DNA evaluation, at least in suspect affected GSDM dogs. We can run the test for people, knowing that it may be negative in a number suspect cases. However, we cannot run it for free since the reagent cost is currently high. We are asking people to make a donation to the University of Florida Foundation with “for Dr. Clemmons’ research” in the memo section and send the check along with a CBC sample on a cold pack to us overnight delivery. The local veterinarian may be able to help you with this. We will provide the results within 2 weeks. We still feel it should not be the sole diagnostic run for the disease, but it may go a long way toward confirming the presence of GSDM. In the future we may be able to reduce the cost by using our Fed Ex number, but this is a start.
Thirdly, we are hoping that we will be able to start stem cell transplantation of bone marrow-derived mesenchymal stem cells early next year. There are several cases with whom we are talking. Our hope is that the stem cells will fix the dogs and necropsies will be a long time off.
We can’t help everyone and we will have to be fairly selective on the imaging and stem cell studies for the moment, but the floodgates are open for sampling DNA. If we can eventually control the costs (by Volume) we might be able to use any remainder of money to help defray the costs for the stem cells.
THYROID CONDITIONS-Dr. Duncan Ferguson - University of Georgia-Grant #2434
AGSDCF funds of $2,000.00 were added to funds from the AKC Canine Health Foundation and other breed entities. Total AKC CHF grant is $97,878
Report received 6/30/2004:
Performance Summary:
Specific Objectives 1 and 2: Amplify the canine TSHB minigene and add sequences and restriction sites to the 5’ and 3’ ends; amplify the canine a sequence and add an immunoaffinity tag on the 3’ end. These steps have been completed.
Specific Objectives 3 and 5: Produce a yoke canine TSH for insertion into the PEAK expression system and express the protein in human embryonic kidney (HEK) cells. These steps have been postponed with efforts directed into cloning sequences into the pBud expression system.
Specific Objective 4: Co-express cTSHB and the a subunit in HEK cells. This step is being developed using pBud vectors.
Specific Objective 6: Purify recombinant cTSH using immunoaffinity columns. This step has begun with efforts currently to increase the expression level by order of magnitude.
Specific Objectives 7 through 11: Assess cross-reactivity with various monoclonal antibodies, assess glycosylation pattern, prepare poyclonal antibody serum, and purify and label the IgG for use in detection systems (tests). Some initial work has begun, but primary efforts await expression and purification of rcTSH 9 steps 4 and 6).
Purdue Bloat Study-Grant Results
Report as of January 6, 2000:
Study was conducted by Dr. Larry Glickman, Purdue University and
was funded by a number of institutions including the AKC Canine Health Foundation, the Morris Animal Foundation, and related breed entities. The research was started in 1994 and various dog shows were visited in March of 1994 to enroll dogs and owners. Over 1,900 dogs were enrolled at more than 25 different shows. The dogs were actively followed by mail and telephone contact with owners until March 31, 1999, when data collection formally ended. Since the volume of the data collected over the 5-year time period is large a complete analysis will require several years. At least 5 publications are planned.
RESULTS so far (further analysis of data will take several years):
The study confirmed that bloat risk increased with advancing age,
larger breed size, greater chest depth/width ratio and having a FIRST DEGREE
relative with a history of bloat. The most significant finding in this study
related to preventive methods used by owners, namely raising the food bowl,
actually INCREASED the risk of bloat by approximately 200%. Other methods
commonly used by owners to prevent bloat including restricting water and
exercise before and after meals were NOT associated with a decrease in the
incidence of bloat.(i.e. they do NOT help prevent bloat!)
Recommendations will be forthcoming once the dietary risk
factors for bloat are assessed in the next phase of the analysis.
CANINE DEGENERATIVE MYELOPATHY:Methionine Suppl.
Grant #1632
Foundation funds were added to funds from the AKC Canine Health
Foundation and other breed entities.
Canine Degenerative Myelopathy: Role of Methionine Supplemenation.
Joan R. Coats, DVM, MS, DACVIM-Neurology
Texas A&M University
Degenerative myelopathy (DM) is a degenerative spinal cord
disease affecting primarily, but not exclusively, older German Shepherd
Dogs. Affected dogs show progressive rear limb weakness and eventually
paralysis. Intestinal abnormalities have been described in affected dogs,
and we suspect that an essential amino acid, methionine, may be deficient
secondary to abnormal intestinal absorption. An imbalance of methionine or
related substances in the blood of spinal fluid may affect the production of
myelin, the fatty covering of the nerves that is essential to their
function. If this is true, dietary supplementation with methionine may halt
neurologic deterioration or improve neurologic signs. Testing blood or
spinal fluid for concentration of methionine and related substances may
allow dogs at risk to receive early treatment before clinical signs of
disease become apparent. Identification of such dogs also could help prevent
them from being used for breeding purposes. Newly established tests of
intestinal function will be used to further characterize abnormalities in
dogs with DM. We also will redefine neurologic-based testing procedures to
monitor disease progression and will utilize modern methods to evaluate the
microscopic characteristics of the disease. We anticipate that the results
of the proposed studies will help assist in the accurate diagnosis and
monitoring of DM, allowing evaluation of new therapies and assisting in the
future identification of a genetic marker for DM.
Started in 1998.
A final report on Grant #1632, the Role of Methionine
Supplementation in treating Degenerative myelopathy (DM) was received in
November of 2002. This was funded jointly with the AKC-CHF by the American
German Sheperd Dog Charitable Foundation, Inc. Principal Investigator was
Joan R. Coats and there were 8 Co-Investigators.
The study tried to see if a Methionine deficiency created DM,
and also studied some other aspects of DM. Results: Methionine
supplementation does not appear to affect neurologic deterioration found in
DM. Thus, it does not help to give dogs Methionine supplementation.
The report stated:
Preliminary data were presented at the 19th Annual American
College of Veterinary Internal Medicine Forum in Denver, CO in 2001 as a
1-hour presentation to the neurology specialty group. Although the results
of this study were disappointing, this presentation was well received as the
FIRST STUDY EVER TO SCIENTIFICALLY ADDRESS EFFICACY OF A SPECIFIC TREATMENT
FOR CANINE DEGENERATIVE MYELOPATHY. The principal investigator and
co-investigators are truly grateful for the opportunity to undertake this
ambitious project and for your generous support from the AKC-CHF and the
American German Shepherd Dog Charitable Foundation, Inc. Through the works
of this project, we have been able to continue our focus toward biochemical,
pathological and inherited studies of canine DM in other breeds.