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

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

Research output: Contribution to journalArticle

108 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Insulin
Relaxin
Testis
Prostate
Nipples
Knockout Mice
Bronchioles
Phenotype
Biological Phenomena
Wild Animals
Peptide Hormones
Pulmonary Fibrosis
Blood Vessels
Fibrosis
Collagen
Parturition
Ligands
Lung
Leydig insulin-like protein
relaxin receptors

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Kamat, A. A., Feng, S., Bogatcheva, N., 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

Genetic targeting of relaxin and insulin-like factor 3 receptors in mice. / Kamat, Aparna A.; Feng, Shu; Bogatcheva, Natalia; Truong, Anne; Bishop, Colin E.; Agoulnik, Alexander I.

In: Endocrinology, Vol. 145, No. 10, 10.2004, p. 4712-4720.

Research output: Contribution to journalArticle

Kamat, AA, Feng, S, Bogatcheva, N, Truong, A, Bishop, CE & Agoulnik, AI 2004, 'Genetic targeting of relaxin and insulin-like factor 3 receptors in mice', Endocrinology, vol. 145, no. 10, pp. 4712-4720. https://doi.org/10.1210/en.2004-0515
Kamat, Aparna A. ; Feng, Shu ; Bogatcheva, Natalia ; Truong, Anne ; Bishop, Colin E. ; Agoulnik, Alexander I. / Genetic targeting of relaxin and insulin-like factor 3 receptors in mice. In: Endocrinology. 2004 ; Vol. 145, No. 10. pp. 4712-4720.
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