Genetic studies of the AMH/MIS signaling pathway for Müllerian duct regression.

Anti-Müllerian hormone (AMH)/Müllerian-inhibiting substance (MIS) is a member of the transforming growth factor-beta (TGF-beta) superfamily. Like other TGF-beta family members, AMH is likely to signal through two transmembrane serine/threonine kinase receptors. Whereas the AMH type II receptor has been clearly defined, only recently has there been evidence about the identity of the AMH type I receptor for Müllerian duct regression in vivo. We generated a new cre mouse line expressing the recombinase in AMH target cells. This line was then used to conditionally inactivate the Bmpr1a gene in the Müllerian duct, resulting in males with a uterus. Thus, Bmpr1a plays an essential role in the process of Müllerian duct regression. To investigate the role of Bmpr1a in granulosa cells, we took advantage of transgenic mice overexpressing human AMH. Surprisingly, these transgenic females that were also conditionally mutant for Bmpr1a in the Müllerian duct had no uterus. These results suggest that when AMH is overexpressed, other TGF-beta family type I receptors can potentially transduce AMH signals.