Genetic targeting of relaxin and insulin-like factor 3 receptors in mice

Aparna A. Kamat, Shu Feng, Natalia V. Bogatcheva, Anne Truong, Colin E. Bishop, Alexander I. Agoulnik

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

Relaxin (RLN) is a small peptide hormone that affects a variety of biological processes. Rln1 knockout mice exhibit abnormal nipple development, prolonged parturition, age-related 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 overespression 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.

Original languageEnglish (US)
Pages (from-to)4712-4720
Number of pages9
JournalEndocrinology
Volume145
Issue number10
DOIs
StatePublished - Oct 2004

ASJC Scopus subject areas

  • Endocrinology

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    Kamat, A. A., Feng, S., Bogatcheva, N. V., Truong, A., Bishop, C. E., & Agoulnik, A. I. (2004). Genetic targeting of relaxin and insulin-like factor 3 receptors in mice. Endocrinology, 145(10), 4712-4720. https://doi.org/10.1210/en.2004-0515