The gene mutated in bare patches and striated mice encodes a novel 3β-hydroxysteroid dehydrogenase
The gene mutated in bare patches and striated mice encodes a novel 3β-hydroxysteroid dehydrogenase
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DOI：
10.1038/9700
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发表时间：
1999-06-01
期刊：
影响因子：
30.8
通讯作者：
Herman, GE
中科院分区：
文献类型：
--
作者：
Liu, XY;Dangel, AW;Herman, GE
在人类和(1)中已经描述了在半合子男性中完全致命的x连锁显性疾病。在这两个物种的小鼠中都没有分离出相关基因；裸斑（Bpa）和条纹（Str）小鼠突变最初是在x射线照射的雄性小鼠的雌性后代中发现的(2)(3)。随后，描述了其他独立等位基因。我们之前已经将这些x连锁的显性男性致死突变定位到一个600 kb的重叠区域，该区域与人类Xq28同源（参考文献4），并在该区间确定了几个候选基因(5)。在这里，我们报道了其中一个编码NAD(P)H类固醇脱氢酶样蛋白的基因Nsdhl在两个独立的Bpa和三个独立的Str等位基因中的突变。受Bpa影响的小鼠组织中固醇的定量分析支持Nsdhl在胆固醇生物合成中的作用。我们的研究结果表明，Bpa和Sfr是等位基因突变，并确定了与x连锁显性、雄性致死表型相关的第一个哺乳动物位点。它们还扩大了与胆固醇代谢异常相关的表型谱。
X-linked dominant disorders that are exclusively lethal prenatally in hemizygous males have been described in human and (1). None of the genes responsible has been isolated in mouse either species; The bare patches (Bpa):and striated (Str) mouse mutations were originally identified in female offspring of X-irradiated males(2) (3). Subsequently, additional independent alleles were described. We have previously mapped these X-linked dominant, male-lethal mutations to an overlapping region:of 600 kb that is homologous to human Xq28 (ref. 4) and identified several candidate genes in this: interval(5). Here we report mutations in one of these genes, Nsdhl, encoding an NAD(P)H steroid dehydrogenase-like protein, in two independent Bpa and three independent Str alleles. Quantitative analysis of sterols from tissues of affected Bpa mice support a role for Nsdhl in cholesterol biosynthesis. Our results demonstrate that Bpa and Sfr are allelic mutations and identify the first mammalian locus associated with an X-linked dominant, male-lethal phenotype. They also expand the spectrum of phenotypes associated with abnormalities of cholesterol metabolism.