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

Endocrinology. 2004 Oct;145(10):4712-20. doi: 10.1210/en.2004-0515. Epub 2004 Jul 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Connective Tissue / pathology
  • Female
  • Fertility
  • Genitalia / pathology
  • Insulin
  • Lung / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mutation
  • Nipples / pathology
  • Phenotype
  • Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology*
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide / genetics
  • Relaxin / physiology*
  • Tissue Distribution


  • Insulin
  • Leydig insulin-like protein
  • Proteins
  • RNA, Messenger
  • RXFP1 protein, mouse
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • Rln1 protein, mouse
  • relaxin receptors
  • Relaxin