Steroid 21-hydroxylase deficiency in mice.

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.