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Zinc deficiency and low enterocyte zinc transporter expression in human patients with autism related mutations in SHANK3

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dc.contributor.author Pfaender, Stefanie
dc.contributor.author Sauer, Ann Katrin
dc.contributor.author Hagmeyer, Simone
dc.contributor.author Mangus, Katharina
dc.contributor.author Linta, Leonhard
dc.contributor.author Liebau, Stefan
dc.contributor.author Bockmann, Juergen
dc.contributor.author Huguet, Guillaume
dc.contributor.author Bourge, Thomas
dc.contributor.author Boeckers, Tobias M.
dc.contributor.author Grabrucker, Andreas M.
dc.date.accessioned 2017-07-27T15:19:06Z
dc.date.available 2017-07-27T15:19:06Z
dc.date.issued 2017
dc.identifier.uri http://hdl.handle.net/10344/5927
dc.description peer-reviewed en_US
dc.description.abstract Phelan McDermid Syndrome (PMDS) is a genetic disorder characterized by features of Autism spectrum disorders. Similar to reports of Zn deficiency in autistic children, we have previously reported high incidence of Zn deficiency in PMDS. However, the underlying mechanisms are currently not well understood. Here, using inductively coupled plasma mass-spectrometry to measure the concentration of Zinc (Zn) and Copper (Cu) in hair samples from individuals with PMDS with 22q13.3 deletion including SHANK3 (SH3 and multiple ankyrin repeat domains 3), we report a high rate of abnormally low Zn/Cu ratios. To investigate possible underlying mechanisms, we generated enterocytes from PMDS patient-derived induced pluripotent stem cells and used Caco-2 cells with knockdown of SHANK3. We detected decreased expression of Zn uptake transporters ZIP2 and ZIP4 on mRNA and protein level correlating with SHANK3 expression levels, and found reduced levels of ZIP4 protein co-localizing with SHANK3 at the plasma membrane. We demonstrated that especially ZIP4 exists in a complex with SHANK3. Furthermore, we performed immunohistochemistry on gut sections from Shank3αβ knockout mice and confirmed a link between enterocytic SHANK3, ZIP2 and ZIP4. We conclude that apart from its well-known role in the CNS, SHANK3 might play a specific role in the GI tract. en_US
dc.language.iso eng en_US
dc.publisher Nature Publishing Group en_US
dc.relation FP7/2007–2013 en_US
dc.relation.ispartofseries Scientific Reorts;7, 45190
dc.relation.uri https://www.nature.com/articles/srep45190
dc.subject homeostasis en_US
dc.subject molecular medicine en_US
dc.subject neuroscience en_US
dc.title Zinc deficiency and low enterocyte zinc transporter expression in human patients with autism related mutations in SHANK3 en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.date.updated 2017-07-27T15:05:59Z
dc.description.version PUBLISHED
dc.identifier.doi 10.1038/srep45190
dc.contributor.sponsor ERC en_US
dc.relation.projectid FP7/2007–2013 en_US
dc.relation.projectid 115300 en_US
dc.relation.projectid 214_A251 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 2710701
dc.internal.copyrightchecked Yes
dc.identifier.journaltitle Scientific Reports
dc.description.status peer-reviewed


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