{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:29:17Z","timestamp":1781105357051,"version":"3.54.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,2,12]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>vacuolated lens<\/jats:italic>\n                    (\n                    <jats:italic>vl<\/jats:italic>\n                    ) mouse mutant causes congenital cataracts and neural tube defects (NTDs), with the NTDs being caused by abnormal neural fold apposition and fusion. Our positional cloning of\n                    <jats:italic>vl<\/jats:italic>\n                    indicates these phenotypes result from a deletion mutation in an uncharacterized orphan G protein-coupled receptor (GPCR),\n                    <jats:italic>Gpr161. Gpr161<\/jats:italic>\n                    displays restricted expression to the lateral neural folds, developing lens, retina, limb, and CNS. Characterization of the\n                    <jats:italic>vl<\/jats:italic>\n                    mutation indicates that C-terminal tail of Gpr161 is truncated, leading to multiple effects on the protein, including reduced receptor-mediated endocytosis. We have also mapped three modifier quantitative trait loci (QTL) that affect the incidence of either the\n                    <jats:italic>vl<\/jats:italic>\n                    cataract or NTD phenotypes. Bioinformatic, sequence, genetic, and functional data have determined that\n                    <jats:italic>Foxe3<\/jats:italic>\n                    , a key regulator of lens development, is a gene responsible for the\n                    <jats:italic>vl<\/jats:italic>\n                    cataract-modifying phenotype. These studies have extended our understanding of the\n                    <jats:italic>vl<\/jats:italic>\n                    locus in three significant ways. One, the cloning of the\n                    <jats:italic>vl<\/jats:italic>\n                    locus has identified a previously uncharacterized GPCR-ligand pathway necessary for neural fold fusion and lens development, providing insight into the molecular regulation of these developmental processes. Two, our QTL analysis has established\n                    <jats:italic>vl<\/jats:italic>\n                    as a mouse model for studying the multigenic basis of NTDs and cataracts. Three, we have identified\n                    <jats:italic>Foxe3<\/jats:italic>\n                    as a genetic modifier that interacts with Gpr161 to regulate lens development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0705657105","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T20:59:53Z","timestamp":1202158793000},"page":"2088-2093","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["The orphan G protein-coupled receptor,\n                    <i>Gpr161<\/i>\n                    , encodes the\n                    <i>vacuolated lens<\/i>\n                    locus and controls neurulation and lens development"],"prefix":"10.1073","volume":"105","author":[{"given":"Paul G.","family":"Matteson","sequence":"first","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jigar","family":"Desai","sequence":"additional","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Korstanje","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Lazar","sequence":"additional","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya E.","family":"Borsuk","sequence":"additional","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarod","family":"Rollins","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindhuja","family":"Kadambi","sequence":"additional","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Joseph","sequence":"additional","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taslima","family":"Rahman","sequence":"additional","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Wink","sequence":"additional","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rym","family":"Benayed","sequence":"additional","affiliation":[{"name":"*Center for Advanced Biotechnology and Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly","family":"Paigen","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609; 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