The in Vivo Roles of Müllerian-inhibiting Substance

This chapter discusses the role of the gonadal hormone, Müllerian-inhibiting substance (MIS), during mammalian sexual differentiation and germ cell development. The chapter also describes in vivo approaches for studying MIS function, especially those utilizing transgenic mice and gene targeting technologies in mouse embryonic stem (ES) cells. MIS actively inhibits the development of the Müllerian ducts, and testosterone induces the differentiation of the Wolffian ducts. The absence of these two hormones during fetal development in the female—the hormonal equivalent of no testes—permits Müllerian duct differentiation and does not induce Wolffian duct development. The chapter describes gain and loss of function in transgenic mice. Experiments are under way to isolate the mouse MIS receptor gene to thereby generate MIS receptor-deficient mice and to compare the phenotype with the MIS gain-of-function and loss-of-function animals.