Mouse mutants of relaxin, insulin-like 3 peptide and their receptors Article

Agoulnik, AI. (2005). Mouse mutants of relaxin, insulin-like 3 peptide and their receptors . Current medicinal chemistry. Immunology, endocrine & metabolic agents, 5(5), 411-419. 10.2174/156801305774322420

cited authors

  • Agoulnik, AI

authors

abstract

  • Recently, mouse mutants of closely related relaxin (Rln1), insulin-like3 (Ins13), and GPCR receptors (Lgr7 and Lgr8/Great) have been produced using gene targeting approach in ES cells and transgenesis. Analysis of their phenotype allowed an identification of the cognate ligand/receptors interactions, specific target organs, and physiological and developmental processes regulated by Rln and Ins13 signaling. Females deficient for Rln1 or Lgr7 exhibit undeveloped mammary gland nipples and increased parturition time during pregnancy. The Rln1 deficiency results in a buildup of fibrosis in different organs and an accumulation of collagen, concurrent with the known effects of Rln1 on extracellular matrix metabolism. Rln1-/- mice have an age-related progression of lung fibrosis with increasing collagen content and concentration, alveolar congestion, and bronchiole epithelium thickening. Male-specific abnormalities were detected in renal and cardiac function of the older Rln1-deficient animals; additionally, poor development of mutant male reproductive organs has been reported. The Ins13-/- or Lgr8-/- male mice exhibit high intraabdominal cryptorchidism. It is caused by the failure of gubernacular ligament differentiation, a structure mediating transabdominal testis descent during male embryogenesis. Transgenic mice with an overexpression of both hormones have been produced; they were instrumental in defining the specificity of Rln1 and Inls3 signaling. Mutant mice provide the experimental models to study the diverse actions of both hormones in vivo. © 2005 Bentham Science Publishers Ltd.

publication date

  • October 1, 2005

published in

Digital Object Identifier (DOI)

start page

  • 411

end page

  • 419

volume

  • 5

issue

  • 5