Chromosomal mapping, isolation, and characterization of the mouse xanthine dehydrogenase gene.

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Xanthine dehydrogenase (XD ) is a key enzyme in the catabolism of purines . A recently isolated XD cDNA clone (Terao et al ., Biochem . J . 283 , 863 -870 , 1992 ) was used to analyze the genomic structure and chromosomal location of this gene . XD was found to be a single -copy gene approximately 70 kb long with 36 exons containing the transcribed sequence . The length of the mouse XD gene was much longer and the structure more complex than those of the Drosophila and Calliphora homologs . The locus encoding the XD gene (designated Xd ) was mapped to the distal part of mouse chromosome 17 by haplotype analysis of 114 interspecific backcross mice . Although Xd inactivation may be responsible for xanthinuria , a rare human genetic disease , this genetic locus is not a candidate for any previously described mouse mutation . The transcription start site was defined by primer extension and RNase mapping analysis , using liver mRNA . No other transcription start sites were identified in the liver and a variety of other organs after treatment with an interferon inducer . Transient transfection analysis in NIH 3 T 3 , tEnd , and COS cells with an appropriate reporter gene demonstrated that a functional promoter is located within the first 268 bp preceding the transcriptional initiation site .