mutations in the slc2a9 gene cause hyperuricosuria and hyperuricemia in the dogslc2a9基因的突变导致hyperuricosuria和高尿酸血的狗.pdfVIP

Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog 1 1 1 1 2 3 Danika Bannasch *, Noa Safra , Amy Young , Nili Karmi , R. S. Schaible , G. V. Ling 1 Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America, 2 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America, 3 Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America Abstract Allantoin is the end product of purine catabolism in all mammals except humans, great apes, and one breed of dog, the Dalmatian. Humans and Dalmatian dogs produce uric acid during purine degradation, which leads to elevated levels of uric acid in blood and urine and can result in significant diseases in both species. The defect in Dalmatians results from inefficient transport of uric acid in both the liver and renal proximal tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal recessive trait for which all Dalmatian dogs are homozygous. Therefore, in order to map the locus, an interbreed backcross was used. Linkage mapping localized the huu trait to CFA03, which excluded the obvious urate transporter 1 gene, SLC22A12. Positional cloning placed the locus in a minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of 333 kb containing only four genes was homozygous in all Dalmatians. Sequence and expression analyses of the SLC2A9 gene indicated three possible mutations, a missense mutation (G616T;C188F) and two promoter mutations