Genetic Targeting of Relaxin and Insulin-Like Factor 3 Receptors in Mice

• Published in: Endocrinology (Philadelphia) 2004-10, Vol.145 (10), p.4712-4720
• Main Authors: Kamat, Aparna A, Feng, Shu, Bogatcheva, Natalia V, Truong, Anne, Bishop, Colin E, Agoulnik, Alexander I
• Format: Article
• Language: English
• Subjects: Abnormalities; Animals; Bioaccumulation; Biological activity; Biological and medical sciences; Connective Tissue - pathology; Female; Females; Fertility; Fibrosis; Fundamental and applied biological sciences. Psychology; Genitalia - pathology; Insulin; Lung - pathology; Lung diseases; Male; Males; Mice; Mice, Knockout; Mice, Transgenic; Mutants; Mutation; Nipples; Nipples - pathology; Parturition; Phenotype; Phenotypes; Prostate; Proteins - metabolism; Receptors; Receptors, Cell Surface - deficiency; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Cell Surface - physiology; Receptors, G-Protein-Coupled; Receptors, Peptide - genetics; Relaxin; Relaxin - physiology; RNA, Messenger - metabolism; Signal transduction; Testes; Tissue Distribution; Transgenic mice; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2004-0515

Relaxin (RLN) is a small peptide hormone that affects a variety of biological processes. Rln1 knockout mice exhibit abnormal nipple development, prolonged parturition, agerelated pulmonary fibrosis, and abnormalities in the testes and prostate. We describe here RLN receptor Lgr7-deficient mice. Mutant females have grossly underdeveloped nipples and are unable to feed their progeny. Some Lgr7−/− females were unable to deliver their pups. Histological analysis of Lgr7 mutant lung tissues demonstrates increased collagen accumulation and fibrosis surrounding the bronchioles and the vascular bundles, absent in wild-type animals. However, Lgr7-deficient males do not exhibit abnormalities in the testes or prostate as seen in Rln1 knockout mice. Lgr7-deficient females with additional deletion of Lgr8 (Great), another putative receptor for RLN, are fertile and have normal-sized litters. Double mutant males have normal-sized prostate and testes, suggesting that Lgr8 does not account for differences in Rln1−/− and Lgr7−/− phenotypes. Transgenic overexpression of Insl3, the cognate ligand for Lgr8, does not rescue the mutant phenotype of Lgr7-deficient female mice indicating nonoverlapping functions of the two receptors. Our data indicate that neither Insl3 nor Lgr8 contribute to the RLN signaling pathway. We conclude that the Insl3/Lgr8 and Rln1/Lgr7 actions do not overlap in vivo.