NULL MUTATION OF THE PROLACTIN RECEPTOR GENE PRODUCES MULTIPLE REPRODUCTIVE DEFECTS IN THE MOUSE

Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heteroz ygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but n ot subsequent, pregnancies. Homozygous females were sterile owing to a complete failure of embryonic implantation. Moreover, they presented multiple reproductive abnormalities, including irregular cycles, reduc ed fertilization rates, defective preimplantation embryonic developmen t, and lack of pseudopregnancy. Half of the homozygous males were infe rtile or showed reduced fertility. This work establishes the prolactin receptor as a key regulator of mammalian reproduction, and provides t he first total ablation model to further study the role of the prolact in receptor and its ligands.