{"id":704,"date":"2017-03-14T11:56:57","date_gmt":"2017-03-14T02:56:57","guid":{"rendered":"http:\/\/www2.med.osaka-u.ac.jp\/wwwmed\/eng\/activities\/results\/2016year\/yamashita-toshihide"},"modified":"2017-04-28T16:13:27","modified_gmt":"2017-04-28T07:13:27","slug":"article14","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2016year\/article14","title":{"rendered":"YAMASHITA Toshihide \u226aMolecular Neuroscience\u226b <span>\u201cA chromosome 16p13.11 microduplication causes hyperactivity through dysregulation of miR-484\/protocadherin-19 signaling\u201d<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li> <a href=\"http:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2016year\/article05\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><!-- \n\n<h1> YAMASHITA Toshihide &lt;Molecular Neuroscience&gt;<\/h1>\n\n --><\/p>\n<p>2016-07-05<br \/>\n  <span class=\"lineFrame\">Publish<\/span>Molecular Psychiatry (2016) doi: 10.1038\/mp.2016.106<\/p>\n<p class=\"figure\"><a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2016\/yamashita20160705eng.jpeg\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2016\/yamashita20160705eng.jpeg\" alt=\"\" height=\"442\" width=\"400\" \/><br \/>\n  <span class=\"click\">Click to enlarge<\/span><\/a><\/p>\n<p><!-- \n\n<h3> A chromosome 16p13.11 microduplication causes hyperactivity through dysregulation of miR-484\/protocadherin-19 signaling<\/h3>\n\n --><\/p>\n<p>Chromosome 16p13.11 microduplication is a risk factor associated with various neurodevelopmental disorders such as attention-deficit\/hyperactivity disorder, intellectual disabilities, developmental delay, and autistic spectrum disorder. The underlying molecular mechanism of this genetic variation remained unknown, but its core genetic locus&mdash;conserved across mice and humans&mdash;contains seven genes. Here, we generated bacterial artificial chromosome-transgenic mice carrying a human 16p13.11 locus, and these mice showed the behavioral hyperactivity phenotype. We identified miR-484 as the responsible gene using a combination of expression and functional analyses. Mature miR-484 was expressed during active cortical neurogenesis, and overexpression of miR-484 decreased proliferation and increased neural progenitor differentiation in vivo. Luciferase screening identified the 3&#8242; untranslated region of protocadherin-19 (Pcdh19) as a target of miR-484. The effect of miR-484 on neurogenesis was rescued by ectopic PCDH19 expression. These results demonstrate that miR-484 promotes neurogenesis by inhibiting PCDH19. Dysregulation of neurogenesis by imbalanced miR-484\/PCDH19 expression contributes to the pathogenesis of 16p13.11 microduplication syndrome.\n<\/p>\n<p><span class=\"lineFrame\">URL<\/span><a href=\"http:\/\/www.med.osaka-u.ac.jp\/pub\/molneu\/index_e.html\" target=\"_blank\">http:\/\/www.med.osaka-u.ac.jp\/pub\/molneu\/index_e.html<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese 2016-07-05 PublishMolecular Psychiatry (2016) doi: 10.1038\/mp.2016.106 Click to enlarge Chrom [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1691,"parent":455,"menu_order":195,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/704"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=704"}],"version-history":[{"count":9,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/704\/revisions"}],"predecessor-version":[{"id":2414,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/704\/revisions\/2414"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/455"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/1691"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=704"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}