{"id":1653,"date":"2022-06-14T20:42:45","date_gmt":"2022-06-14T20:42:45","guid":{"rendered":"http:\/\/carola.wwwnl1-sr12.supercp.com\/?p=1653"},"modified":"2023-01-13T11:44:54","modified_gmt":"2023-01-13T11:44:54","slug":"reversible-symptome","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/de\/reversible-symptome\/","title":{"rendered":"Reversible Symptome bei M\u00e4usen"},"content":{"rendered":"<p><strong>Prof. Huda Zoghbi et al. (Baylor College of Medicine, Texas, USA) haben in der Zeitschrift Nature einen Artikel mit dem Titel \"Reversibler Ph\u00e4notyp bei M\u00e4usen durch Einsatz von genetischer Rettung oder Antisense-Oligonukleotiden\" ver\u00f6ffentlicht. In diesem Artikel werden die Ergebnisse der Verwendung von Antisense-Oligonukleotiden (ASO) bei der Korrektur des MeCP2-Spiegels und der Umkehrung von Verhaltensst\u00f6rungen, molekularen und elektrophysiologischen St\u00f6rungen in einem Tiermodell mit einer MECP2-Genduplikation vorgestellt.<\/strong><\/p>\n\n\n\n<p>Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides, Huda Zoghbi <em>et al,<\/em> <em>Natur<\/em><strong> 528,&nbsp;<\/strong>123-126 (2015)<\/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>ZUSAMMENFASSUNG DES ARTIKELS (Aus dem Englischen \u00fcbersetzt):<\/strong><\/p>\n\n\n\n<p>Eine Variation der Kopienzahl wurde h\u00e4ufig mit Entwicklungsverz\u00f6gerungen, geistiger Behinderung und einem autistischen Spektrum in Verbindung gebracht. Das MECP2-Genduplikationssyndrom ist eine Neuordnung des Genoms, die vor allem m\u00e4nnliche Personen betrifft und durch ein autistisches Spektrum, geistige Behinderung, motorische Dysfunktion, Angstzust\u00e4nde, epileptische Anf\u00e4lle, Infektionen des Atmungssystems und einen fr\u00fchen Tod gekennzeichnet ist.<\/p>\n\n\n\n<p>Die gro\u00dfe Vielfalt der Defizite, die durch die \u00dcberexpression des MeCP2-Proteins verursacht werden, stellt eine gro\u00dfe Herausforderung f\u00fcr herk\u00f6mmliche Therapieans\u00e4tze dar, die auf biochemischen Wegen beruhen. Daher haben wir therapeutische Strategien untersucht, die direkt auf das MeCP2-Protein abzielen und das Potenzial haben, in die klinische Therapie \u00fcbertragen zu werden.<\/p>\n\n\n\n<p>Die erste Frage, mit der wir uns befassten, war, ob die neurologische Dysfunktion nach dem Auftreten von Symptomen umkehrbar ist. Die Umkehrung der Ph\u00e4notypen bei symptomatischen erwachsenen M\u00e4usen wurde in einigen Modellen des monogenen Verlusts neurologischer Funktionen nachgewiesen, insbesondere beim Verlust von MeCP2 beim Rett-Syndrom. Dies deutet darauf hin, dass zumindest in einigen F\u00e4llen die Neuroanatomie ausreichend intakt bleiben kann, so dass die Korrektur der diesen St\u00f6rungen zugrunde liegenden molekularen Dysfunktion eine gesunde Physiologie wiederherstellen kann.<\/p>\n\n\n\n<p>Da beim MECP2-Duplikationssyndrom keine Neurodegeneration auftritt, gehen wir davon aus, dass die Wiederherstellung normaler MeCP2-Spiegel bei erwachsenen M\u00e4usen mit MECP2-Duplikation zu einer Korrektur ihres Ph\u00e4notyps f\u00fchren sollte.<\/p>\n\n\n\n<p>Durch die Erzeugung und Charakterisierung eines Mecp2-\u00fcberexprimierenden Mausmodells zeigen wir hier, dass die Korrektur der MeCP2-Spiegel die Defizite im Verhalten, auf molekularer und elektrophysiologischer Ebene weitgehend umkehrt.<\/p>\n\n\n\n<p>Wir reduzierten MeCP2 auch mithilfe einer Antisense-Oligonukleotid-Strategie, die ein gr\u00f6\u00dferes Translationspotenzial hat.<\/p>\n\n\n\n<p>Antisense-Oligonukleotide sind kleine, modifizierte Nukleins\u00e4uren, die selektiv mit der von einem Zielgen transkribierten Boten-RNA hybridisieren und diese stumm schalten k\u00f6nnen, und wurden erfolgreich zur Korrektur von Defiziten in verschiedenen Mausmodellen eingesetzt.<\/p>\n\n\n\n<p>Wir stellen fest, dass die Antisense-Oligonukleotide eine weitgehende Wiederherstellung des Ph\u00e4notyps in symptomatischen transgenen erwachsenen M\u00e4usen mit MECP2-Duplikation induzieren und die MeCP2-Spiegel dosisabh\u00e4ngig in lymphoblastoiden Zellen von Patienten mit MECP2-Duplikation korrigieren.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<p><\/p>\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-white-color has-text-color has-background wp-element-button\" href=\"https:\/\/www.nature.com\/articles\/nature16159\" style=\"border-radius:14px;background-color:#f7a13f\" target=\"_blank\" rel=\"noreferrer noopener\">Zur Publikation<\/a><\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Pr. Huda Zoghbi et al. (Baylor College of Medicine, Texas, USA) ont publi\u00e9 un article dans la revue Nature intitul\u00e9 \u00abPh\u00e9notype r\u00e9versible chez la souris par l\u2019utilisation de sauvetage g\u00e9n\u00e9tique [&hellip;]<\/p>","protected":false},"author":1,"featured_media":6890,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8],"tags":[],"class_list":["post-1653","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 la souris - 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\/de\/reversible-symptome\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Sympt\u00f4mes r\u00e9versibles chez la souris - DupMECP2\" \/>\n<meta property=\"og:description\" content=\"Pr. 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