{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:35:18Z","timestamp":1791326118521,"version":"4.3.1"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,9]],"date-time":"2006-01-09T00:00:00Z","timestamp":1136764800000},"content-version":"vor","delay-in-days":253,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> We studied ligand\u2010receptor interactions between relaxin (RLN), insulin\u2010like 3 peptide (INSL3), and LGR7 and LGR8 receptors. The phenotypic effects of deficiency for <jats:italic>Lgr7<\/jats:italic> and <jats:italic>Lgr8<\/jats:italic> receptors, transgenic overexpression of <jats:italic>Rln1<\/jats:italic> and <jats:italic>Insl3<\/jats:italic>, and different combinations of these mutations in mice were analyzed. It was reported that <jats:italic>Rln1<\/jats:italic>\u2010deficient mice exhibit abnormal nipple development, prolonged parturition, age\u2010related 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\u2010deficient males do not exhibit abnormalities of male reproductive organs as seen in Rln1 knockout mice. Double\u2010mutant males deficient for <jats:italic>Lgr7<\/jats:italic> and <jats:italic>Lgr8<\/jats:italic> have a normal prostate, suggesting that Lgr8 does not account for differences in <jats:italic>Rln1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Lgr7<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> phenotypes. We also produced mice with transgenic overexpression of <jats:italic>Rln1<\/jats:italic> under rat insulin 2 promoter. Rln1 transgenic females exhibited increased nipple size, whereas <jats:italic>Rln1<\/jats:italic> transgenic females deficient in <jats:italic>Lgr7<\/jats:italic> 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 <jats:italic>Insl3<\/jats:italic> does not rescue the mutant phenotype of <jats:italic>Lgr7<\/jats:italic>\u2010deficient mice, suggesting the non\u2010overlapping functions of two signaling pathways. In summary, our data indicate that the Insl3\/Lgr8 and Rln1\/Lgr7 pathways are distinct and separate <jats:italic>in vivo<\/jats:italic>. Therefore, we propose to rename Lgr8 as Insl3r (Insl3 receptor) and Lgr7 as Rlnr (relaxin receptor).<\/jats:p>","DOI":"10.1196\/annals.1282.012","type":"journal-article","created":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T09:26:55Z","timestamp":1118827615000},"page":"82-90","source":"Crossref","is-referenced-by-count":18,"title":["Genetic Targeting of Relaxin and Insl3 Signaling in Mice"],"prefix":"10.1111","volume":"1041","author":[{"given":"SHU","family":"FENG","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NATALIA V.","family":"BOGATCHEVA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"APARNA A.","family":"KAMAT","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ALEXANDER I.","family":"AGOULNIK","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,9]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2004.00481.x"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065654"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200398200"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.13.5.0272"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/10364"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.1029"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.19.2309"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.14.8.0510"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.1.6404"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212457200"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1120fje"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0096"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.16.2.0772"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0013"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000079784.81186.B9"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0449fje"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00663-6"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00628.x"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0515"},{"key":"e_1_2_10_21_2","unstructured":"Feng S. A.A. Kamat N.V. Bogatcheva et al.2004. Endocrine effects of transgenic relaxin in mice. Submitted for publication."},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/315115a0"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1282.012","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1282.012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T09:08:10Z","timestamp":1695632890000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1282.012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,5]]}},"alternative-id":["10.1196\/annals.1282.012"],"URL":"https:\/\/doi.org\/10.1196\/annals.1282.012","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5]]}}}