The Keeshond Club of America has helped fund several grants, through the generosity of its members. Members have the opportunity to donate money to the KCA Health Fund each year when they return their dues notice. This money is turned over to the AKC Canine Health Foundation KEESHOND DONOR ADVISED FUND at the end of the year. It is earmarked for research involving our breed. When a proposal comes forth, that impacts the Keeshond, upon recommendation of the Health Committee, KCA releases the funds to go toward the study. The studies funded, in part, by KCA are:

Active Grant No: 631: The Genome Wide Search for the Genetic Cause of Primary Hyperparathyroidism in the KEESHOND: Richard E. Goldstein, DVM

GRANT 631: Primary hyperparathyroidism (PHPT) is a disease that causes increased concentrations of calcium in the blood of older dogs. This disease can affect dogs of many breeds, with the highest incidence in Keeshonden. We believe that PHPT in the Keeshond is a hereditable disease caused by a defect in a single gene. We have collected DNA from a large number of affected and older non-affected Keeshonden and determined that PHPT is hereditable in the Keeshond. We have recently evaluated 3 genes most frequently involved in human PHPT, to see if defects could be found in these genes in affected Keeshonden. Our results indicate that these genes are not the cause of familial PHPT in Keeshonden. Therefore this proposed study includes searching the entire genome 2for the region of the PHPT defect in Keeshonden. This will be accomplished by comparing markers spread throughout the DNA between affected and non-affected Keeshonden. A successful conclusion of this study will provide an accurate genetic test enabling early detection of Keeshonden carrying the gene responsible for PHPT. Once the affected area in the gene has been identified, other breeds can be tested to define the genetic cause of PHPT in those breeds as well.

UPDATE to GRANT 631: http://www.akcchf.org/news/index.cfm?article_id=145., Researchers Closer to Cause of Primary Hyperparathyroidism in the Keeshond [Tuesday, May 16, 2006]

Pending Grant No. 372: Determination of Breed-Specific Reference Intervals for Assessing Thyroid Function in Golden Retrievers, Samoyeds and KEESHONDEN: Rebecca L. Davies, PHD, University of Minnesota

GRANT 372: The thyroid gland secretes hormones which are very important for development, growth, reproduction and metabolism. Sometimes the thyroid gland does not produce enough thyroid hormone and hypothyroidism occurs. Hypothyroidism is very common in dogs and many are treated with thyroid hormone supplementation. This disease occurs frequently in Alaskan Malamutes, English Setters, Golden Retrievers, Keeshonden, Samoyeds, and Siberian Huskies. Hypothyroidism is generally diagnosed by measuring the concentration of thyroid hormones in serum. This concentration is then compared to a reference interval derived from measurements of thyroid hormone concentration in samples taken from large groups of normal dogs. Generally this works very well, however, in some breeds, the true reference range is lower than the range determined when dogs of various breeds (or mixed-breeds) are analyzed. Breed-specific thyroid hormone reference intervals have only been determined in a few breeds. Without breed-specific intervals, inappropriate use of general values may result in healthy dogs being misclassified as hypothyroid. These animals may be incorrectly placed on thyroid supplementation, and unnecessarily removed from breeding programs. Furthermore, the incidence of hypothyroidism in the breed will be overestimated. We wish to establish breed-specific normal thyroid reference intervals to improve the diagnosis of true hypothyroidism in the Alaskan Malamute, English Setter, Golden Retriever, Keeshond, Samoyed, and Siberian Husky breeds.

Pending Grant No. 266: Canine Epilepsy: Mapping the Genes and Developing a Linkage Test : Drs. J. Mickelson and N. Patterson; University of Minnesota.

Grant 266: We seek to continue our molecular genetic studies to develop a screening linkage test for predicting epilepsy in Beagles, English Springer Spaniels, and Vizslas and to institute new studies in Welsh Springer Spaniels, Greater Swiss Mountain Dogs, Irish Setters, Otterhounds, Samoyeds and Keeshonden. Preliminary results of our genetic marker studies indicate that we will be able to find linked markers and the chromosomal segment containing the epilepsy gene given sufficiently large and informative pedigrees. The late age of onset of seizures in dogs with epilepsy means that a dog has often already been bred before it is diagnosed as affected. In some individuals seizures are well controlled with anticonvulsant medications. However, a significant number of dogs have "refractory" seizures needing high doses of medications to achieve control or the severity of seizures may be such that the owner elects to have the dog euthanized. Our genome mapping approach to identifying the regions of the canine genome containing the defective genes will ultimately lead to genetic tests for epilepsy that would allow breeders to screen potential breeding animals for this common, frustrating, and potentially devastating disorder.

(Another interesting site concerning Epilepsy research is: http://www.canine-epilepsy.net.)

Completed Grant No. 1275: Markers for Canine Homologues of Three Human Chromosomes: Gary S. Johnson, DVM, PhD; University of Missouri, Columbia

Grant 1275: This project sought to identify candidate genes for specific diseases in dogs. Candidate genes are genes known to cause specific diseases in other species. The researchers searched for canine equivalents of three human chromosomes. They identified more than 25 Type I markers (markers that are associated with specific genes). These markers, mapped on the canine genome linkage map, provide valuable information to other scientists looking for the genes causing various heritable diseases in dogs.

Pending Grant No. 2434: Recombinant Thyrotropin (TSH): Standard for the Next Generation of Canine TSH Immunoassays with Improved Sensitivity : Duncan Ferguson, VMD, PhD; University of Georgia

Grant 2434: Hypothyroidism, a failure of the thyroid gland, is the most common hormonal abnormality in dogs, causing a variety of medical problems in many breeds, including hair loss and skin infections. The measurement of serum levels of the pituitary hormone thyrotropin (TSH) has been used as a reliable and sensitive screening test for thyroid glandular insufficiency in human medicine for many years, but the �first generation� assays for canine TSH (cTSH) are missing as many as 1 out of 4 cases of hypothyroidism, resulting in no improvement in diagnostic sensitivity compared to total T4 measurement. Furthermore, the available assays have not been sensitive enough to distinguish low values of cTSH from those in the normal range. Towards the goal of improving current and future immunoassay sensitivity based upon a pure recombinant canine TSH (cTSH) hormone standard, our laboratory has succeeded in cloning and sequencing the two peptide subunits of canine TSH and have expressed them in small quantities. Using techniques recently developed in our parallel work on equine TSH, we plan to express and purify recombinant canine TSH in high quantities and validate its use as a pure immunoassay standard to facilitate its worldwide use.

Pending Grant No. 305: Histocompatibility Alleles Conferring Susceptibility to Canine Diabetes, Immune-Mediated Thyroiditis and Immune-Mediated Hemolytic Anemia: Dr. Wayne Potts, University of Utah

Grant 305: Autoimmune diseases cause significant amounts of mortality and debilitating disease in dogs. In humans many autoimmune diseases occur only in individuals expressing one of the few predisposing histocompatibility genes. For example, all cases of type I diabetes in humans are associated with only a few of the many alleleic forms of class II histocompatibility genes. Consequently, if the frequencies of these few alleles were reduced by half, the incidence of diabetes would be reduced by half. Here we propose to characterize histocompatibility susceptibility alleles for three major, heritable canine autoimmune diseases - diabetes, immune-mediated thyroiditis and immune-mediated hemolytic anemia. If any of these three debilitating (or lethal) autoimmune diseases have a restricted number of susceptibility alleles it will allow: (1) development of diagnostic tests for identifying individuals at risk for prophylactic therapy and research and (2) reducing the incidence of the disease by reducing the breeding of individuals carrying the predisposing histocompatibility alleles. For each of the three autoimmune diseases, we propose to collect DNA samples from approximately 100 purebred dogs diagnosed with the disease. Histocompatibility genes will be cloned and sequenced for each dog for a total of approximately 1100 sequences. Histocompatibility alleles will be tested for significant associations with each of the autoimmune diseases.

It is the active participation of all Keeshond lovers, through monetary donations and submitting research information, canine DNA, blood, etc that helps research to succeed and enables us to find solutions regarding Keeshond health related problems.

To learn more about these research grants, go to the AKC Canine Health Foundation website (http://www.akcchf.org and click on the link to Sponsored Research � Grants by Breed). You may also contact the research veterinarian at his respective University.