Gotoh H, Sagai T, Hata J, Shiroishi T, Moriwaki K
Department of Cell Genetics, National Institute of Genetics, Shizuoka-ken, Japan.
Endocrinology. 1988 Oct;123(4):1923-7. doi: 10.1210/endo-123-4-1923.
The enzyme steroid 21-hydroxylase (21-OHase) plays a key role in adrenal steroidogenesis. Defects in this enzyme are responsible for one of the most common inborn errors of metabolism in humans. Duplicated genes for the enzyme are located in the class III region of the major histocompatibility complex (MHC), HLA. In the mouse, the genes encoding 21-OHase have been mapped to the homologous region of the H-2 complex. We previously described an H-2 recombinant haplotype aw18, in which the gene for the complement component C4 and one of the two genes for 21-OHase in the H-2 class III region have been deleted. We now report that newborn aw18 homozygous mice are deficient in 21-OHase activity, and that homozygosity for the aw18 haplotype directly causes death at the early postnatal stage. Morphological changes in the adrenal glands of newborn aw18 homozygotes are also observed. The aw18 recombinant haplotype is expected to serve as a useful and, thus far, unique experimental system to study adrenal steroidogenesis in vivo and as an animal model for the inherited human disease of congenital adrenal hyperplasia.
类固醇21-羟化酶（21-OHase）在肾上腺类固醇生成中起关键作用。该酶的缺陷是人类最常见的先天性代谢缺陷之一。该酶的重复基因位于主要组织相容性复合体（MHC）HLA的III类区域。在小鼠中，编码21-OHase的基因已定位到H-2复合体的同源区域。我们之前描述了一种H-2重组单倍型aw18，其中H-2 III类区域中的补体成分C4基因和两个21-OHase基因之一已被删除。我们现在报告，新生的aw18纯合子小鼠缺乏21-OHase活性，并且aw18单倍型的纯合性直接导致出生后早期死亡。还观察到新生aw18纯合子肾上腺的形态学变化。aw18重组单倍型有望作为一种有用的、且迄今为止独特的实验系统，用于体内研究肾上腺类固醇生成，并作为先天性肾上腺增生这一遗传性人类疾病的动物模型。
