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Null Mutation of the Prolactin Receptor Gene Produces a Defect in Maternal Behavior

Institut National de la Santé et de la Recherche Médicale Unit 344 (B.K.L., N.B., P.A.K.), Endocrinologie Moléculaire, Faculté de Médecine Necker, 75730 Paris Cedex 15, France; Cancer Research Program (C.J.O.), Garvan Institute of Medical Research, Darlinghurst NSW2010, Sydney, Australia; and Tufts University School of Veterinary Medicine (R.S.B.), Department of Biomedical Sciences, North Grafton, Massachusetts 01536

Address all correspondence and requests for reprints to: Brian Lucas, INSERM Unit 344, Faculté de Médecine Necker, 156 rue de Vaugirard 75730 Paris Cedex 15, France. E-mail: lucas{at}necker.fr

We have studied pup-directed maternal behavior in mice carrying a germ line null mutation of the PRL receptor (PRLR) gene. Homozygous mutant and heterozygous mutant nulliparous females show a deficiency in pup-induced maternal behavior. Moreover, primiparous heterozygous females exhibit a profound deficit in maternal care when challenged with foster pups. Morris maze studies revealed normal configural learning in the heterozygous and homozygous animals. Eating, locomotor activity, sexual behavior, and exploration (all processes regulated by the hypothalamus) are normal in PRLR mutant mice. Olfactory function was tested in an aversive conditioning paradigm, results indicating that heterozygous and homozygous PRLR mutant mice are not anosmic. These studies clearly establish the PRLR as a regulator of maternal behavior.

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