We have used gene targeting to generate relaxin (rlx)-deficient mice. The majority (15 of 17) of homozygous (rlx Ϫ/Ϫ ) mice are fertile and produce normal litters. However their mammary development is deficient; pups are unable to suckle and die within 24 h of birth unless cross-fostered to a wild-type (rlx ϩ/ϩ ) foster mother. The nipples of rlx Ϫ/Ϫ animals do not enlarge significantly during pregnancy, and their histology retains the appearance of the virgin state. Breast parenchyma is

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... t underdeveloped at term even though milk is produced. Mammary ducts become grossly dilated in these animals. Heterozygous (rlx ϩ/Ϫ ) mice lactate normally. The interpubic ligament does not relax during pregnancy in rlx Ϫ/Ϫ mice. Plasma osmolality during late gestation was significantly higher (P Ͻ 0.001) in rlx Ϫ/Ϫ mice than in wild-type controls. (Endocrinology 140: [445][446][447][448][449][450][451][452][453] 1999)