Grant Amount: $12,960

Dr. Paula S. Henthorn, PhD, University of Pennsylvania

February 1, 2011 - July 31, 2011

Sponsor(s): Danny's Fund, Mastiff Club of America, Mastiff Club of America Charitable Trust

Breed(s): Bulldog, Irish Terrier, Mastiff, Scottish Deerhound

Disease(s): Cystinuria

Project Summary

Cystinuria is an inherited disorder that causes kidney and urinary tract stones in dog, man and other animals and has been documented in over 60 breeds of dogs. In humans, mutations in the protein-coding regions of two genes are found in affected individuals. In some dog breeds, cystinuria is an autosomal recessive trait caused by mutations in one of the cystinuria genes. However, in many dog breeds, the genetic basis of cystinuria is much more complex. Our most recent data indicates that 1) in Mastiffs and a second breed, DNA changes near one of the "cystinuria genes" are associated with cystine stone formation, usually before 4 years of age (dogs that have a later age of stone formation may have a genetically distinct form), and 2) that gender and reproductive status affects the level cystine and dibasic amino acid levels in the urine. We have identified several markers near one of the cystinuria genes that can be used to predict dogs at risk for early stone formation, and will continue to evaluate their usefulness for genetic testing. While we have not yet identified any sequence changes that could be responsible for the effect of neutering on urine amino acid levels, this effect occurs in several breeds, which will help us continue our studies to gain a better understanding of this frustrating disease. Our goal continues to be the development of DNA tests that can be used to identify dogs at greatest risk of cystine stone formation, and for choosing mating pairs that will produce puppies at lower risk for cystine stone formation.