{"id":1648,"date":"2022-06-14T20:42:45","date_gmt":"2022-06-14T20:42:45","guid":{"rendered":"http:\/\/carola.wwwnl1-sr12.supercp.com\/?p=1648"},"modified":"2023-01-13T11:44:56","modified_gmt":"2023-01-13T11:44:56","slug":"phenotype-reversible-souris-humanisees","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/el\/phenotype-reversible-souris-humanisees\/","title":{"rendered":"\u0391\u03bd\u03b1\u03c3\u03c4\u03c1\u03ad\u03c8\u03b9\u03bc\u03b1 \u03c3\u03c5\u03bc\u03c0\u03c4\u03ce\u03bc\u03b1\u03c4\u03b1 \u03c3\u03b5 \u03b5\u03be\u03b1\u03bd\u03b8\u03c1\u03c9\u03c0\u03b9\u03c3\u03bc\u03ad\u03bd\u03b1 \u03c0\u03bf\u03bd\u03c4\u03af\u03ba\u03b9\u03b1"},"content":{"rendered":"<p><strong>Shao et al. du groupe du Pr. Zoghbi (Baylor College of Medicine, Texas, USA) ont publi\u00e9 un article dans la revue Science Translational medicine intitul\u00e9 \u00abTh\u00e9rapie par oligonucl\u00e9otides antisens dans un mod\u00e8le murin humanis\u00e9 du syndrome de duplication de MECP2\u00bb. <\/strong><\/p>\n\n\n\n<p><strong>Chaque esp\u00e8ce a des g\u00e8nes qui lui sont propres. Les g\u00e8nes codent pour des prot\u00e9ines sp\u00e9cifiques \u00e0 chaque esp\u00e8ce. Il est possible que les prot\u00e9ine humaines et murines soient l\u00e9g\u00e8rement diff\u00e9rentes. Le model utilis\u00e9 dans les travaux pr\u00e9sent\u00e9s, appel\u00e9 \u00ab&nbsp;mod\u00e8le humanis\u00e9&nbsp;\u00bb, permet d\u2019\u00e9valuer plus l\u2019activit\u00e9 d\u2019oligonucl\u00e9otides antisens (ASO) sp\u00e9cifiquement sur la prot\u00e9ine humaine produite par une souris. Il se rapproche donc plus de l\u2019utilisation future de l\u2019ASO chez l\u2019humain.<\/strong><\/p>\n\n\n\n<p><strong>L\u2019article pr\u00e9sente les r\u00e9sultats obtenus apr\u00e8s injection intrac\u00e9r\u00e9broventriculaire d\u2019ASO sur le mod\u00e8le murin de duplication du g\u00e8ne \u00ab\u00a0humanis\u00e9 MECP2\u00a0\u00bb dans lequel la souris porte deux all\u00e8les MECP2 humains et aucun all\u00e8le endog\u00e8ne de souris.<\/strong><\/p>\n\n\n\n<p><strong>L\u2019administration a permis de r\u00e9duire efficacement l&rsquo;expression de MeCP2 dans tout le cerveau de ces souris, a att\u00e9nu\u00e9 plusieurs d\u00e9ficits comportementaux, et a restaur\u00e9 l&rsquo;expression de certains g\u00e8nes r\u00e9gul\u00e9s par MeCP2 de mani\u00e8re dose-d\u00e9pendante et sans aucune toxicit\u00e9.<\/strong><\/p>\n\n\n\n<p>\u0398\u03b5\u03c1\u03b1\u03c0\u03b5\u03af\u03b1 \u03bc\u03b5 \u03bf\u03bb\u03b9\u03b3\u03bf\u03bd\u03bf\u03c5\u03ba\u03bb\u03b5\u03bf\u03c4\u03af\u03b4\u03b9\u03b1 \u03b1\u03bd\u03c4\u03b9-\u03b1\u03bd\u03c4\u03b9-\u03c3\u03c5\u03bd\u03b5\u03af\u03b4\u03b7\u03c3\u03b7\u03c2 \u03c3\u03b5 \u03ad\u03bd\u03b1 \u03b5\u03be\u03b1\u03bd\u03b8\u03c1\u03c9\u03c0\u03b9\u03c3\u03bc\u03ad\u03bd\u03bf \u03bc\u03bf\u03bd\u03c4\u03ad\u03bb\u03bf \u03c0\u03bf\u03bd\u03c4\u03b9\u03ba\u03bf\u03cd \u03c4\u03bf\u03c5 \u03c3\u03c5\u03bd\u03b4\u03c1\u03cc\u03bc\u03bf\u03c5 \u03b4\u03b9\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03bf\u03cd \u03c4\u03bf\u03c5 MECP2, Shao et al.<em>Sci. Transl. Med<\/em>. <strong>13<\/strong>, 7785 (2021)<\/p>\n\n\n\n<p><\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<p><\/p>\n\n\n\n<p><strong>RESUM\u00c9&nbsp;DE L&rsquo;ARTICLE (Traduit de l&rsquo;anglais) :<\/strong><\/p>\n\n\n\n<p>De nombreux troubles conduisant \u00e0 une d\u00e9ficience intellectuelle sont dus \u00e0 des variations du nombre de copies et, \u00e0 ce jour, aucune option th\u00e9rapeutique n&rsquo;a \u00e9t\u00e9 test\u00e9e pour cette cat\u00e9gorie de maladies. Le syndrome de duplication MECP2 est l&rsquo;un des r\u00e9arrangements g\u00e9nomiques les plus courants chez les hommes et r\u00e9sulte de duplications couvrant le locus du g\u00e8ne de la prot\u00e9ine de liaison m\u00e9thyl-CpG 2 (MECP2). Nous avons pr\u00e9c\u00e9demment d\u00e9montr\u00e9 que la th\u00e9rapie par oligonucl\u00e9otide antisens (ASO) peut r\u00e9duire la quantit\u00e9 de prot\u00e9ine MECP2 dans un mod\u00e8le de souris avec la duplication et inverser les sympt\u00f4mes caract\u00e9ristiques du syndrome.<\/p>\n\n\n\n<p>Ce mod\u00e8le de souris \u00e9tait cependant porteur d&rsquo;un all\u00e8le humain transg\u00e9nique et d&rsquo;un all\u00e8le de souris, ce dernier \u00e9tant prot\u00e9g\u00e9 du ciblage par L\u2019ASO-MECP2 sp\u00e9cifique \u00e0 l&rsquo;homme.<\/p>\n\n\n\n<p>La prot\u00e9ine MeCP2 est une prot\u00e9ine dont la concentration est importante. L&rsquo;ASO doit donc \u00eatre titr\u00e9 de mani\u00e8re \u00e0 ce que la quantit\u00e9 de MeCP2 ne soit pas trop r\u00e9duite car ceci provoquerait le syndrome de Rett. Par cons\u00e9quent, nous avons g\u00e9n\u00e9r\u00e9 un mod\u00e8le de duplication du g\u00e8ne \u00ab\u00a0humanis\u00e9 MECP2\u00a0\u00bb dans lequel la souris porte deux all\u00e8les MECP2 humains et aucun all\u00e8le endog\u00e8ne de souris. L&rsquo;injection intrac\u00e9r\u00e9broventriculaire de l\u2019ASO-MECP2 a permis de r\u00e9duire efficacement l&rsquo;expression de MeCP2 dans tout le cerveau de ces souris. De plus, l\u2019ASO-MECP2 a att\u00e9nu\u00e9 plusieurs d\u00e9ficits comportementaux et a restaur\u00e9 l&rsquo;expression de certains g\u00e8nes r\u00e9gul\u00e9s par MeCP2 de mani\u00e8re dose-d\u00e9pendante et sans aucune toxicit\u00e9. L&rsquo;administration de l\u2019ASO-MECP2 dans le syst\u00e8me nerveux central est donc bien tol\u00e9r\u00e9e et b\u00e9n\u00e9fique dans ce mod\u00e8le de souris et constitue une approche transposable qui pourrait \u00eatre envisageable pour le traitement des syndromes de duplication du g\u00e8ne MECP2.<\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button is-style-fill\"><a class=\"wp-block-button__link has-background wp-element-button\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33658357\/\" style=\"border-radius:14px;background-color:#f7a13f\" target=\"_blank\" rel=\"noreferrer noopener\">\u0394\u03b5\u03af\u03c4\u03b5 \u03c4\u03b7 \u03b4\u03b7\u03bc\u03bf\u03c3\u03af\u03b5\u03c5\u03c3\u03b7<\/a><\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Shao et al. du groupe du Pr. Zoghbi (Baylor College of Medicine, Texas, USA) ont publi\u00e9 un article dans la revue Science Translational medicine intitul\u00e9 \u00abTh\u00e9rapie par oligonucl\u00e9otides antisens dans [&hellip;]<\/p>","protected":false},"author":1,"featured_media":11722,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8],"tags":[],"class_list":["post-1648","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Sympt\u00f4mes r\u00e9versibles chez les souris humanis\u00e9es - DupMECP2<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/dupmecp2.eu\/el\/phenotype-reversible-souris-humanisees\/\" \/>\n<meta property=\"og:locale\" content=\"el_GR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Sympt\u00f4mes r\u00e9versibles chez les souris humanis\u00e9es - DupMECP2\" \/>\n<meta property=\"og:description\" content=\"Shao et al. du groupe du Pr. 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