TY - JOUR
T1 - Müllerian-inhibiting substance function during mammalian sexual development
AU - Behringer, Richard R.
AU - Finegold, Milton J.
AU - Cate, Richard L.
N1 - Funding Information:
Correspondence should be addressed to R. R. B. We thank Jenny Deng and Helen Lu for technical assistance; Allan Bradley for the AB-1 ES and SNL 76/7 ST0 cell lines; Philippe Soriano, Alian Bradley, and the members of their laboratories for helpful discus:sions; Nathalie Josso, Martin Matzuk, and Yuji Mishina for review of the manuscript; and Richard Palmiter and Ralph Brinster for their enthusiasm and encouragement. This research was supported by National Institutes of Health grant HD30284 and by the Sid W. Richardson Foundation (R. R. B.). Mice carrying the MIS mutation have been dleposited in the Induced Mutant Resource at the Jackson Laboratory, Bar Harbor, ME. This project is dedicated to the memory of Alfred Jost, who first hypothesized the existence of I’hormone inhibitrice.
PY - 1994/11/4
Y1 - 1994/11/4
N2 - 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 differentation 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.
AB - 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 differentation 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.
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U2 - 10.1016/0092-8674(94)90251-8
DO - 10.1016/0092-8674(94)90251-8
M3 - Article
C2 - 7954809
AN - SCOPUS:0028172159
SN - 0092-8674
VL - 79
SP - 415
EP - 425
JO - Cell
JF - Cell
IS - 3
ER -