Watanabe T, Ihara N, Itoh T, Fujita T, Sugimoto Y
Shirakawa Institute of Animal Genetics, Odakura, Nishigo, Nishi-shirakawa, Fukushima 961-8061, Japan.
J Biol Chem. 2000 Jul 21;275(29):21789-92. doi: 10.1074/jbc.C000230200.
Defective xanthine dehydrogenase (XDH) activity in humans results in xanthinuria and xanthine calculus accumulation in kidneys. Bovine xanthinuria was demonstrated in a local herd and characterized as xanthinuria type II, similar to the Drosophila ma-l mutations, which lose activities of molybdoenzymes, XDH, and aldehyde oxidase, although sulfite oxidase activity is preserved. Linkage analysis located the disease locus at the centromeric region of bovine chromosome 24, where a ma-l homologous, putative molybdopterin cofactor sulfurase gene (MCSU) has been physically mapped. We found that a deletion mutation at tyrosine 257 in MCSU is tightly associated with bovine xanthinuria type II.
人类中黄嘌呤脱氢酶（XDH）活性缺陷会导致黄嘌呤尿症以及肾脏中黄嘌呤结石的积累。在当地一群牛中发现了牛黄嘌呤尿症，其特征为II型黄嘌呤尿症，类似于果蝇的ma-l突变，该突变会丧失钼酶、XDH和醛氧化酶的活性，不过亚硫酸盐氧化酶活性得以保留。连锁分析将该疾病基因座定位在牛24号染色体的着丝粒区域，在该区域已通过物理定位确定了一个与ma-l同源的假定钼蝶呤辅因子硫酸化酶基因（MCSU）。我们发现MCSU中酪氨酸257处的缺失突变与牛II型黄嘌呤尿症紧密相关。
