Genetic targeting of relaxin and insulin-like factor 3 receptors in mice.
Relaxin (RLN) is a small peptide hormone that affects a variety of biological processes. Rln1 knockout mice exhibit abnormal nipple development, prolonged parturition, agerelated 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 overexpression 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.
Kamat
Aparna A
AA
Department of Obstetrics and Gynecology, 6550 Fannin Street, Baylor College of Medicine, Houston, Texas 77030, USA.
Feng
Shu
S
Bogatcheva
Natalia V
NV
Truong
Anne
A
Bishop
Colin E
CE
Agoulnik
Alexander I
AI
D000818:Animals; D003238:Connective Tissue / Q000473:pathology; D005260:Female; D005298:Fertility; D005835:Genitalia / Q000473:pathology; D007328:Insulin; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009558:Nipples / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000235:genetics; D012065:Relaxin / Q000502:physiology*; D014018:Tissue Distribution
D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D012333:RNA, Messenger; C478103:RXFP1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C492607:Rln1 protein, mouse; C033395:relaxin receptors; D012065:Relaxin