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

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 NIH3T3, 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.