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. 1993 Dec 1;90(23):11162–11166. doi: 10.1073/pnas.90.23.11162

Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene.

D B Lubahn 1, J S Moyer 1, T S Golding 1, J F Couse 1, K S Korach 1, O Smithies 1
PMCID: PMC47942  PMID: 8248223

Abstract

Estrogen receptor and its ligand, estradiol, have long been thought to be essential for survival, fertility, and female sexual differentiation and development. Consistent with this proposed crucial role, no human estrogen receptor gene mutations are known, unlike the androgen receptor, where many loss of function mutations have been found. We have generated mutant mice lacking responsiveness to estradiol by disrupting the estrogen receptor gene by gene targeting. Both male and female animals survive to adulthood with normal gross external phenotypes. Females are infertile; males have a decreased fertility. Females have hypoplastic uteri and hyperemic ovaries with no detectable corpora lutea. In adult wild-type and heterozygous females, 3-day estradiol treatment at 40 micrograms/kg stimulates a 3- to 4-fold increase in uterine wet weight and alters vaginal cornification, but the uteri and vagina do not respond in the animals with the estrogen receptor gene disruption. Prenatal male and female reproductive tract development can therefore occur in the absence of estradiol receptor-mediated responsiveness.

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