International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


12:00 – 12:15 HRS


Agoulnik A
Baylor College of Medicine

Co-Authors: Kamat A, Feng S, Bogatcheva N, Bishop C
Institutions: Baylor College of Medicine

Relaxins are peptide hormones produced primarily in reproductive organs. In the mouse, there are two relaxin genes, Rln1 and Rln3 that encode related peptides with an overlapping pattern of expression. Deletion of relaxin-1 in mice causes remodeling of connective tissues in several organs. Recently, biochemical studies have identified two closely related G protein-coupled receptors (LGR7 and LGR8/GREAT) as putative receptors for relaxins. Additionally, insulin-like factor 3 has been identified as a cognate ligand for Lgr8, but not for Lgr7. We have shown that the Lgr7 receptor is expressed in a variety of murine organs including reproductive organs, brain, heart, aorta, etc. Using insertional gene targeting approach, we targeted the lacZ gene into the mouse Lgr7 locus. Lgr7 deficient mice have abnormal mammary development with smaller, poorly developed nipples. Mutant females are unable to deliver milk to their pups and have significantly prolonged length of parturition compared to littermates. Examination of sections of the lung in Lgr7 deficient mice reveals pulmonary fibrosis. Examination of collagen content using trichrome staining of histological sections reveals increased collagen deposition in several mutant tissues. We have also produced mice with a deficiency of both Lgr7 and Lgr8 receptors, as well as Lgr7 deficient mice with an additional transgenic copy of Insl3. Analysis of their phenotype did not reveal additional phenotypic abnormalities, indicating a non-overlapping nature of the relaxin and Insl3 signaling in vivo. Relaxin receptor mutant mice provide a useful model of fibrosis development in several organs.

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