| HOME SCHEDULE AUTHOR INDEX SUBJECT INDEX |
|
(307) GENETIC TARGETING OF RELAXIN SIGNALING IN MICE. Agoulnik, Alexander 1, Kamat, Aparna1, Feng, Shu1, Bogatcheva, Natalia1, Bishop, Colin1, 2, 1 Baylor College of Medicine, Houston, TX2 Baylor College of Medicine, Houston, TX ABSTRACT- Relaxin (RLN) is a small peptide hormone that affects a variety of biological processes in vivo. Rln1 knockout mice exhibit abnormal nipple development, prolonged parturition, age-related pulmonary fibrosis, and abnormalities in the testis and prostate. Two putative relaxin seven transmembrane receptors, LGR7 and LGR8/GREAT, have been identified recently. Mutation of Lgr8/Great of its cognate ligand Insl3 in mice causes cryptorchidism. Using gene targeting approach we produced now mice deficient for Lgr7 receptor. Mutant females have grossly underdeveloped nipples and are unable to feed their progeny. Parturition is prolonged in these females resulting in significantly higher number of dead pups. Histological analysis of Lgr7 mutant lung tissues demonstrates increased collagen accumulation and peri-venular smooth muscle hypertrophy. However, Lgr7-deficient males do not exhibit abnormalities of male reproductive organs as seen in Rln1 knockout mice. Double mutant males deficient for Lgr7 and Lgr8/Great have normal prostate, suggesting that Lgr8 does not account for differences in Rln1-/- and Lgr7-/- phenotypes. Double mutant males exhibit increased incidence of unilateral torsion or necrosis of the cryptorchid testis. Transgenic overexpression of Insl3 does not rescue the mutant phenotype of Lgr7-deficient mice indicating non-overlapping functions of two receptors. We also produced mice with transgenic overexpression of Rln1. Rln1 transgenic females exhibit increased nipple size, whereas Rln transgenic females deficient for Lgr7 have underdeveloped nipples. In summary, our data indicate that the Insl3/Lgr8 and Rln1/Lgr7 signaling pathways do not overlap in vivo. KEY WORDS: insulin-like factor 3, Lgr8 receptor, relaxin, Lgr7 receptor |
