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

TLDR

The study aims to establish the prolactin receptor as a key regulator of mammalian reproduction and to provide the first complete ablation model for further investigation of its ligands. The authors generated mice with a germ‑line null mutation of the prolactin receptor gene via embryonic stem cell gene targeting. Heterozygous females exhibited near‑complete lactation failure after the first pregnancy, while homozygous females were sterile due to implantation failure and displayed irregular cycles, reduced fertilization, defective pre‑implantation development, and absent pseudopregnancy; homozygous males had reduced fertility or were infertile.

Abstract

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.