{"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":"reversibler-phanotyp-vermenschlichte-mause","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/de\/reversibler-phanotyp-vermenschlichte-mause\/","title":{"rendered":"Reversible Symptome bei humanisierten M\u00e4usen"},"content":{"rendered":"<p><strong>Shao et al. aus der Gruppe von Prof. Zoghbi (Baylor College of Medicine, Texas, USA) ver\u00f6ffentlichten in der Zeitschrift Science Translational medicine einen Artikel mit dem Titel \"Antisense-Oligonucleotid-Therapie in einem humanisierten Mausmodell des MECP2-Duplikationssyndroms\". <\/strong><\/p>\n\n\n\n<p><strong>Jede Art hat Gene, die f\u00fcr sie typisch sind. Die Gene kodieren f\u00fcr Proteine, die f\u00fcr jede Art spezifisch sind. Es ist m\u00f6glich, dass sich menschliche und murine Proteine leicht unterscheiden. Das in der vorliegenden Arbeit verwendete Modell, das als \"humanisiertes Modell\" bezeichnet wird, erm\u00f6glicht es, die Aktivit\u00e4t von Antisense-Oligonukleotiden (ASO) spezifisch auf das von einer Maus produzierte menschliche Protein zu untersuchen. Es ist daher n\u00e4her an der zuk\u00fcnftigen Verwendung von ASO beim Menschen.<\/strong><\/p>\n\n\n\n<p><strong>Der Artikel stellt die Ergebnisse vor, die nach intrazerebroventrikul\u00e4rer Injektion von ASO im Mausmodell der \"humanisierten MECP2\"-Genduplikation erzielt wurden, bei dem die Maus zwei menschliche MECP2-Allele und kein endogenes Maus-Allel tr\u00e4gt.<\/strong><\/p>\n\n\n\n<p><strong>Die Verabreichung reduzierte wirksam die MeCP2-Expression im gesamten Gehirn dieser M\u00e4use, milderte mehrere Verhaltensdefizite und stellte die Expression einiger durch MeCP2 regulierter Gene dosisabh\u00e4ngig und ohne jegliche Toxizit\u00e4t wieder her.<\/strong><\/p>\n\n\n\n<p>Antisense oligonucleotide therapy in a humanized mouse model of MECP2 duplication syndrome, 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>ARTIKELZUSAMMENFASSUNG (Aus dem Englischen \u00fcbersetzt) :<\/strong><\/p>\n\n\n\n<p>Viele St\u00f6rungen, die zu geistiger Behinderung f\u00fchren, sind auf Ver\u00e4nderungen der Kopienzahl zur\u00fcckzuf\u00fchren, und bislang wurden f\u00fcr diese Kategorie von Krankheiten noch keine Therapieoptionen getestet. Das MECP2-Duplikationssyndrom ist eine der h\u00e4ufigsten genomischen Neuordnungen bei M\u00e4nnern und resultiert aus Duplikationen, die den Genlocus des Methyl-CpG-Bindungsproteins 2 (MECP2) abdecken. Wir haben zuvor gezeigt, dass die Therapie mit Antisense-Oligonukleotiden (ASO) die Menge des MECP2-Proteins in einem Mausmodell mit der Duplikation reduzieren und die charakteristischen Symptome des Syndroms umkehren kann.<\/p>\n\n\n\n<p>Dieses Mausmodell war jedoch Tr\u00e4ger eines transgenen menschlichen Allels und eines Mausallels, wobei letzteres vor dem Targeting durch das humanspezifische ASO-MECP2 gesch\u00fctzt war.<\/p>\n\n\n\n<p>Das Protein MeCP2 ist ein Protein mit einer hohen Konzentration. ASO muss daher so titriert werden, dass die Menge an MeCP2 nicht zu stark reduziert wird, da dies das Rett-Syndrom ausl\u00f6sen w\u00fcrde. Daher erzeugten wir ein \"humanisiertes MECP2\"-Genduplikationsmodell, bei dem die Maus zwei menschliche MECP2-Allele und kein endogenes Maus-Allel tr\u00e4gt. Durch die intrazerebroventrikul\u00e4re Injektion von ASO-MECP2 konnte die Expression von MeCP2 im gesamten Gehirn dieser M\u00e4use wirksam reduziert werden. Dar\u00fcber hinaus milderte ASO-MECP2 mehrere Verhaltensdefizite und stellte die Expression bestimmter durch MeCP2 regulierter Gene dosisabh\u00e4ngig und ohne jegliche Toxizit\u00e4t wieder her. Die Verabreichung von ASO-MECP2 in das zentrale Nervensystem ist daher in diesem Mausmodell gut vertr\u00e4glich und vorteilhaft und stellt einen \u00fcbertragbaren Ansatz dar, der f\u00fcr die Behandlung von Syndromen mit MECP2-Genduplikation in Frage kommen k\u00f6nnte.<\/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\">Zur Publikation<\/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\/de\/reversibler-phanotyp-vermenschlichte-mause\/\" \/>\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 les souris humanis\u00e9es - DupMECP2\" \/>\n<meta property=\"og:description\" content=\"Shao et al. du groupe du Pr. 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