TY - JOUR
T1 - Genetic targeting of relaxin and Insl3 signaling in mice
AU - Feng, Shu
AU - Bogatcheva, Natalia V.
AU - Kamat, Aparna A.
AU - Agoulnik, Alexander I.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2005
Y1 - 2005
N2 - We studied ligand-receptor interactions between relaxin (RLN), insulin-like 3 peptide (INSL3), and LGR7 and LGR8 receptors. The phenotypic effects of deficiency for Lgr7 and Lgr8 receptors, transgenic overexpression of Rln1 and Insl3, and different combinations of these mutations in mice were analyzed. It was reported that Rln1-deficient mice exhibit abnormal nipple development, prolonged parturition, age-related pulmonary fibrosis, and abnormalities in the testis and prostate. Mutation of Lgr8 or its cognate ligand Insl3 causes cryptorchidism. Mutant females deficient for the Lgr7 receptor have grossly undeveloped nipples and are unable to feed their progeny. Parturition is prolonged in these females, resulting in a significantly higher number of stillborn pups. Histologic analysis of Lgr7 mutant lung tissues demonstrates increased collagen accumulation and perivenular 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 have a normal prostate, suggesting that Lgr8 does not account for differences in Rln1-/- and Lgr7-/- phenotypes. We also produced mice with transgenic overexpression of Rln1 under rat insulin 2 promoter. Rln1 transgenic females exhibited increased nipple size, whereas Rln1 transgenic females deficient in Lgr7 had undeveloped nipples, indicating that Lgr7 is the only receptor for relaxin that mediates this effect. Transgenic overexpression of Rln1 does not affect gonadal descent in females, and transgenic overexpression of Insl3 does not rescue the mutant phenotype of Lgr7-deficient mice, suggesting the non-overlapping functions of two signaling pathways. In summary, our data indicate that the Insl3/Lgr8 and Rln1/Lgr7 pathways are distinct and separate in vivo. Therefore, we propose to rename Lgr8 as Insl3r (Insl3 receptor) and Lgr7 as Rlnr (relaxin receptor).
AB - We studied ligand-receptor interactions between relaxin (RLN), insulin-like 3 peptide (INSL3), and LGR7 and LGR8 receptors. The phenotypic effects of deficiency for Lgr7 and Lgr8 receptors, transgenic overexpression of Rln1 and Insl3, and different combinations of these mutations in mice were analyzed. It was reported that Rln1-deficient mice exhibit abnormal nipple development, prolonged parturition, age-related pulmonary fibrosis, and abnormalities in the testis and prostate. Mutation of Lgr8 or its cognate ligand Insl3 causes cryptorchidism. Mutant females deficient for the Lgr7 receptor have grossly undeveloped nipples and are unable to feed their progeny. Parturition is prolonged in these females, resulting in a significantly higher number of stillborn pups. Histologic analysis of Lgr7 mutant lung tissues demonstrates increased collagen accumulation and perivenular 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 have a normal prostate, suggesting that Lgr8 does not account for differences in Rln1-/- and Lgr7-/- phenotypes. We also produced mice with transgenic overexpression of Rln1 under rat insulin 2 promoter. Rln1 transgenic females exhibited increased nipple size, whereas Rln1 transgenic females deficient in Lgr7 had undeveloped nipples, indicating that Lgr7 is the only receptor for relaxin that mediates this effect. Transgenic overexpression of Rln1 does not affect gonadal descent in females, and transgenic overexpression of Insl3 does not rescue the mutant phenotype of Lgr7-deficient mice, suggesting the non-overlapping functions of two signaling pathways. In summary, our data indicate that the Insl3/Lgr8 and Rln1/Lgr7 pathways are distinct and separate in vivo. Therefore, we propose to rename Lgr8 as Insl3r (Insl3 receptor) and Lgr7 as Rlnr (relaxin receptor).
KW - Gene targeting
KW - Insl3
KW - Lgr7
KW - Lgr8/Great
KW - Relaxin
UR - http://www.scopus.com/inward/record.url?scp=23644438200&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23644438200&partnerID=8YFLogxK
U2 - 10.1196/annals.1282.012
DO - 10.1196/annals.1282.012
M3 - Article
C2 - 15956690
AN - SCOPUS:23644438200
SN - 0077-8923
VL - 1041
SP - 82
EP - 90
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -