Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse

Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse
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DOI:
10.1101/gad.11.2.167
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发表时间:
1997-01-15
影响因子:
10.5
通讯作者:
Kelly, PA
Kelly, PA
中科院分区:
生物学1区
文献类型:
--
作者:
Ormandy, CJ;Camus, A;Kelly, PA

文献摘要

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携带催乳素受体基因的生殖系无效突变的小鼠已经通过胚胎干细胞中的基因靶向产生。杂合子女性表现出几乎完全失败的哺乳期大大减少乳腺发育后,他们的第一次,但不是随后的,怀孕。纯合子雌性由于胚胎植入完全失败而不育。此外,他们提出了多种生殖异常,包括不规则的周期,受精率降低,植入前胚胎发育缺陷,缺乏假孕。一半的纯合男性不育或生育能力下降。这项工作确立了催乳素受体作为哺乳动物生殖的关键调节因子,并提供了第一个全面的消融模型,以进一步研究催乳素受体及其配体的作用。
Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heterozygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but not subsequent, pregnancies. Homozygous females were sterile owing to a complete failure of embryonic implantation. Moreover, they presented multiple reproductive abnormalities, including irregular cycles, reduced fertilization rates, defective preimplantation embryonic development, and lack of pseudopregnancy. Half of the homozygous males were infertile or showed reduced fertility. This work establishes the prolactin receptor as a key regulator of mammalian reproduction, and provides the first total ablation model to further study the role of the prolactin receptor and its ligands.