Our laboratory has cloned 3 genes critical to uric acid synthesis in mammals. They include hypoxanthine-guanine phosphoribosyl transferase (HPRT), phosphoribosylpyrophosphate (PRPP) synthetase and urate oxidase. Rapid diagnostic methods have been developed which will enable the identification of point mutations in the HPRT gene which is associated with Lesch-Nyhan (L-N) syndrome in human patients.We have succeeded in the isolation for a 2.3 kb cDNA for PRPP synthetase from pig. The DNA sequence determined from the coding region shows a high degree of homology with the cDNA sequence recently determined from rat.The enzyme urate oxidase catalyzes the oxidation of uric acid to allantoin in all mammals except humans and certain primates. Recently, mice with complete HPRT deficiency have been identified. These animals display none of the neurological symptoms observed in human patients. This has raised the possibility that the absence of urate oxidase activity in man may contribute to the neurological symptoms observed in L-N patients. A 2.2 kb cDNA for urate oxidase has been isolated from a porcine liver A cDNA library. Although humans demonstrate no urate oxidase activity, analysis of human genomic DNA has revealed the presence of homologous sequences in human. The loss of urate oxidase activity in human is probably due to a lack of gene transcription since a Northern analysis detects no urate oxidase mRNA in human liver.
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