Implications of multiple phenotypes observed in prolactin receptor knockout mice

The development of a mouse line deficient in the PRL receptor (PRLR) would be an ideal means to better understand the multiple functions of prolactin. We were worried initially that removal of the PRLR from the mouse genome m ight be lethal and were surprised to find this not to be the case. We ident ified numerous deficiencies in PRLR knockout (KO) animals. Female homozygou s mice are completely infertile and lack normal mammary development, while hemizogotes are unable to lactate following their first pregnancy. PRLR KO males and females have markedly elevated (30- to 100-fold) serum prolactin levels and in some instances pituitary hyperplasia is present. Maternal beh avior is severely affected in both hemizygous and heterozygous animals. Bon e formation is reduced in young animals and adults (males and females). Rec ently, we noticed that older KO animals show a slight reduction in body wei ght which appears to be due to reduced abdominal fat deposition.