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Affected individuals exhibit growth failure, intellectual disability and a broad spectrum of developmental malformations. Among them, renal agenesis or hypoplasia, decreased innervation of the gut, and ptosis are consistent with impaired Ret signaling. Ret is a receptor tyrosine kinase that achieves full activity when recruited to lipid rafts. Mice mutant for <jats:italic>Ret<\/jats:italic> are born with no kidneys and enteric neurons, and display sympathetic nervous system defects causing ptosis. Since cholesterol is a critical component of lipid rafts, here we tested the hypothesis of whether the cause of the above malformations found in SLOS is defective Ret signaling owing to improper lipid raft composition or function. No defects consistent with decreased Ret signaling were found in newborn <jats:italic>Dhcr7<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, or in <jats:italic>Dhcr7<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice lacking one copy of <jats:italic>Ret<\/jats:italic>. Although kidneys from <jats:italic>Dhcr7<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice showed a mild branching defect <jats:italic>in vitro<\/jats:italic>, GDNF was able to support survival and downstream signaling of sympathetic neurons. Consistently, GFR\u03b11 correctly partitioned to lipid rafts in brain tissue. Finally, replacement experiments demonstrated that 7-DHC efficiently supports Ret signaling <jats:italic>in vitro<\/jats:italic>. Taken together, our findings do not support a role of Ret signaling in the pathogenesis of SLOS.<\/jats:p>","DOI":"10.1038\/srep28534","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T18:17:46Z","timestamp":1466705866000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndrome"],"prefix":"10.1038","volume":"6","author":[{"given":"Myriam","family":"Gou-F\u00e0bregas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Maci\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Anerillas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Vaquero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariona","family":"Jov\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Jain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Ribera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Encinas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,6,23]]},"reference":[{"key":"BFsrep28534_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/ejhg.2008.10","volume":"16","author":"FD Porter","year":"2008","unstructured":"Porter, F. 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