Behringer R R, Finegold M J, Cate R L
Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Cell. 1994 Nov 4;79(3):415-25. doi: 10.1016/0092-8674(94)90251-8.
To investigate the role of Müllerian-inhibiting substance (MIS) in mammalian sexual development, we generated MIS-deficient mice. Although MIS-deficient males had testes that were fully descended and produced functional sperm, they also developed female reproductive organs, which interfered with sperm transfer into females, rendering most of these males infertile. Their testes had Leydig cell hyperplasia and, in one instance, neoplasia. The actions of the two primary hormones of male sexual differentiation were genetically eliminated using the testicular feminization (Tfm) mutation in combination with the MIS mutant allele. XY Tfm/MIS double mutants developed as females, with a uterus, coiled oviducts, and no male reproductive organs except undescended dysfunctional testes. These results suggest that eliminating the presumptive female reproductive tract in male fetuses facilitates fertility and that in testes MIS is a negative regulator of Leydig cell proliferation. Eliminating the presumptive male reproductive tract is necessary for proper oviductal morphogenesis during female mouse development.
为了研究苗勒管抑制物质（MIS）在哺乳动物性别发育中的作用，我们培育出了MIS缺陷型小鼠。尽管MIS缺陷型雄性小鼠的睾丸完全下降并能产生功能性精子，但它们也发育出了雌性生殖器官，这干扰了精子向雌性体内的输送，导致这些雄性小鼠大多不育。它们的睾丸出现了莱迪希细胞增生，在一个案例中还出现了肿瘤。利用睾丸雌性化（Tfm）突变与MIS突变等位基因相结合，从基因层面消除了雄性性别分化的两种主要激素的作用。XY Tfm/MIS双突变体发育为雌性，有子宫、盘绕的输卵管，除了未下降的功能失调睾丸外没有雄性生殖器官。这些结果表明，消除雄性胎儿中假定的雌性生殖道有助于生育，并且在睾丸中MIS是莱迪希细胞增殖的负调节因子。消除假定的雄性生殖道对于雌性小鼠发育过程中输卵管的正常形态发生是必要的。
