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dc.contributor.authorGou Fàbregas, Myriam
dc.contributor.authorMacià Armengol, Anna
dc.contributor.authorAnerillas, Carlos
dc.contributor.authorVaquero, Marta
dc.contributor.authorJové Font, Mariona
dc.contributor.authorJain, Sanjay
dc.contributor.authorRibera i Calvet, Joan
dc.contributor.authorEncinas Martín, Mario
dc.description.abstractSmith-Lemli-Opitz syndrome (SLOS) is a rare disorder of cholesterol synthesis. 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 Ret 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 Dhcr7−/− mice, or in Dhcr7−/− mice lacking one copy of Ret. Although kidneys from Dhcr7−/− mice showed a mild branching defect in vitro, GDNF was able to support survival and downstream signaling of sympathetic neurons. Consistently, GFRα1 correctly partitioned to lipid rafts in brain tissue. Finally, replacement experiments demonstrated that 7-DHC efficiently supports Ret signaling in vitro. Taken together, our findings do not support a role of Ret signaling in the pathogenesis of SLOS.ca_ES
dc.description.sponsorshipThis work was supported by grants from Fundació La Marató de TV3 (101810), and from Ministerio de Economía y Competitividad (BFU2010-17628 and BFU2013-47175), and funding from Suport als Grups de Recerca (2014 SGR 138) from Generalitat de Catalunya to ME. MG-F was supported by a grant from Fundació La Marató de TV3. AM was supported by a predoctoral fellowship from Universitat de Lleida. C A is supported by a predoctoral contract from Universitat de Lleida. MV was supported by a predoctoral fellowship from AGAUR (Generalitat de Catalunya).ca_ES
dc.publisherNature Publishing Groupca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofScientific Reports, 2016, vol. 2016, vol. 6, núm. 28534ca_ES
dc.rightscc-by (c) Gou et al., 2016
dc.title7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndromeca_ES

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