Genetic studies of the AMH/MIS signaling pathway for Mullerian duct regression
Genetic studies of the AMH/MIS signaling pathway for Mullerian duct regression
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DOI：
10.1016/j.mce.2003.09.006
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发表时间：
2003-12-15
影响因子：
4.1
通讯作者：
Behringer, RR
中科院分区：
文献类型：
--
作者：
Jamin, SP;Arango, NA;Behringer, RR
抗苗勒管激素（AMH）/苗勒管抑制物质（MIS）是转化生长因子-β（TGF-β）超家族的成员。与其他TGF-P家族成员一样，AMH可能通过两个跨膜丝氨酸/苏氨酸激酶受体发出信号。虽然AMH II型受体已被明确定义，但直到最近才有证据表明AMH I型受体在体内与苗勒管退行有关。我们产生了一个新的cre小鼠系表达重组酶的AMH靶细胞。然后用这条线在苗勒管中有条件地扩增Bmpr 1a基因，从而产生具有子宫的男性。因此，Bmpr 1a在苗勒管退化过程中起着至关重要的作用。为了研究Bmpr 1a在颗粒细胞中的作用，我们利用过表达人AMH的转基因小鼠。令人惊讶的是，这些转基因女性，也有条件突变的Bmpr 1a在苗勒管没有子宫。这些结果表明，当AMH过度表达时，其他TGF-β家族I型受体可能会抑制AMH信号。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Anti-Mullerian hormone (AMH)/Mullerian-inhibiting substance (MIS) is a member of the transforming growth factor-beta (TGF-beta) superfamily. Like other TGF-P 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 Mullerian duct regression in vivo. We generated a new cre mouse line ex pressing the recombinase in AMH target cells. This line was then used to conditionally inactivate the Bmpr1a gene in the Mullerian duct, resulting in males with a uterus. Thus, Bmpr1a plays an essential role in the process of Mullerian 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 Mullerian duct had no uterus. These results suggest that when AMH is overexpressed, other TGF-beta family type I receptors can potentially transduce AMH signals. (C) 2003 Elsevier Ireland Ltd. All rights reserved.