Dalmatian bladder stones caused by gene that regulates uric acid in humans

A gene mutation in Dalmatian dogs causing high levels of uric acid that can lead to bladder stones has been identified by a team of researchers in the School of Veterinary Medicine at the University of California, Davis.

The discovery equips dog breeders with the tools to eliminate the harmful trait from the Dalmatian breed, and yields clues to the cause of similar problems in humans. The findings are published November 7 in the open-access journal PLoS Genetics.

All mammals excrete waste products in their urine, but only humans, great apes and Dalmatian dogs produce elevated levels of uric acid in their urine and blood. Other dog breeds do not usually produce uric acid.

In humans, this can result in kidney stones, hypertension and gout, a painful inflammation of the joints. In Dalmatians, high uric acid levels result in the formation of bladder stones that often have to be removed surgically.

"This defect has been reported for nearly a century and was probably unintentionally introduced as breeders worked to select more distinctive spotting patterns," said veterinary geneticist and lead author Danika Bannasch. The gene responsible, however, has remained elusive until now.

"This trait can now be removed from the breed by crossing Dalmatians with the normal offspring of the original Dalmatian-pointer breeding that occurred in the early 1970s," Bannasch said. "The result is a healthy dog that looks like a Dalmatian, maintains the Dalmatian breed characteristics and is genetically almost identical."

The researchers collected DNA and urine samples from hundreds of dogs to identify the gene responsible for high levels of uric acid. Genetic analysis of dogs that are a cross between pointers and Dalmatians revealed that gene to be SLC2A9, a gene that recently has been reported to be important in regulating uric acid levels in humans. DNA analysis showed that mutations in the SLC2A9 gene were responsible for the elevated uric acid in the Dalmatians.

Although humans also carry the SLC2A9 gene, scientists have not yet identified the exact mechanism that causes humans and great apes to have elevated uric acid levels. The recent identification of the responsible gene mutation in dogs may help scientists better understand the related problem in humans.

The study was partially supported by a fellowship from the Morris Animal Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases within the National Institutes of Health.

By Dec. 1, the Veterinary Genetics Laboratory in UC Davis¹ School of Veterinary Medicine will begin offering DNA testing for the mutation in dogs to allow breeders to eliminate the trait. Information on the testing program will be available online at http://www.vgl.ucdavis.edu/.

PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.pgen.1000246 (link will go live on Friday, November 7)

CITATION: Bannasch D, Safra N, Young A, Karmi N, Schaible RS, et al. (2008) Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog. PLoS Genet 4(11): e1000246. doi:10.1371/journal.pgen.1000246

Danika Bannasch
Veterinary Medicine
(530) 754-8728
dlbannasch@ucdavis.edu

Pat Bailey
News Service
(530) 752-9843
pjbailey@ucdavis.edu

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