Mouse Mutants of Relaxin, Insulin-Like 3 Peptide and their Receptors

Author(s): A. I. Agoulnik.

Journal Name: Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents

Volume 5 , Issue 5 , 2005

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Abstract:

Recently, mouse mutants of closely related relaxin (Rln1), insulin-like3 (Insl3), 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 Insl3 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 Insl3-/- 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.

Keywords: relaxin, insulin-like, lgr, gene targeting, mouse mutations

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Article Details

VOLUME: 5
ISSUE: 5
Year: 2005
Page: [411 - 419]
Pages: 9
DOI: 10.2174/156801305774322420
Price: $58

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