{"id":9394,"date":"2022-06-14T20:42:45","date_gmt":"2022-06-14T18:42:45","guid":{"rendered":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/"},"modified":"2024-11-04T21:53:13","modified_gmt":"2024-11-04T20:53:13","slug":"inversione-dei-fenotipi-nei-topi-con-duplicazione-di-mecp2","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/it\/inversione-dei-fenotipi-nei-topi-con-duplicazione-di-mecp2\/","title":{"rendered":"Inversione dei fenotipi nei topi con duplicazione di MECP2"},"content":{"rendered":"<p><strong>Il Prof. Huda Zoghbi e altri (Baylor College of Medicine, Texas, USA) hanno pubblicato un articolo sulla rivista Nature dal titolo \"Reversible phenotype in mice using gene rescue or antisense oligonucleotides\". L'articolo presenta i risultati dell'uso di oligonucleotidi antisenso per correggere i livelli di MeCP2 e invertire i disturbi comportamentali, molecolari ed elettrofisiologici in un modello animale con una duplicazione del gene MECP2.<\/strong><\/p>\n\n\n\n<p>Inversione dei fenotipi nei topi con duplicazione di MECP2 mediante salvataggio genetico o oligonucleotidi antisenso, Huda Zoghbi <em>e altri,<\/em> <em>Natura<\/em><strong> 528, <\/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>ESTRATTO DELLA PUBBLICAZIONE:<\/strong><\/p>\n\n\n\n<p>Le variazioni del numero di copie sono state frequentemente associate a ritardi nello sviluppo, disabilit\u00e0 intellettiva e disturbi dello spettro autistico. La sindrome da duplicazione di MECP2 \u00e8 uno dei riarrangiamenti genomici pi\u00f9 comuni nei maschi ed \u00e8 caratterizzata da autismo, disabilit\u00e0 intellettiva, disfunzioni motorie, ansia, epilessia, infezioni ricorrenti del tratto respiratorio e morte precoce.<\/p>\n\n\n\n<p>L'ampia gamma di deficit causati dalla sovraespressione della methyl-CpG-binding protein 2 (MeCP2) rappresenta una sfida scoraggiante per i tradizionali approcci terapeutici basati sulle vie biochimiche. Di conseguenza, abbiamo cercato strategie che avessero come bersaglio diretto MeCP2 e che potessero essere tradotte in terapia clinica.<\/p>\n\n\n\n<p>La prima domanda che ci siamo posti \u00e8 se la disfunzione neurologica sia reversibile dopo l'insorgenza dei sintomi. L'inversione dei fenotipi nei topi adulti sintomatici \u00e8 stata dimostrata in alcuni modelli di disordini neurologici monogenici con perdita di funzione, tra cui la perdita di MeCP2 nella sindrome di Rett, indicando che, almeno in alcuni casi, la neuroanatomia pu\u00f2 rimanere sufficientemente intatta in modo che la correzione della disfunzione molecolare alla base di questi disturbi possa ripristinare una fisiologia sana.<\/p>\n\n\n\n<p>Data l'assenza di neurodegenerazione nella sindrome da duplicazione di MECP2, proponiamo che il ripristino dei normali livelli di MeCP2 nei topi adulti con duplicazione di MECP2 possa salvare il loro fenotipo.<\/p>\n\n\n\n<p>Generando e caratterizzando un modello murino condizionato di sovraespressione di Mecp2, dimostriamo che la correzione dei livelli di MeCP2 inverte in larga misura i deficit comportamentali, molecolari ed elettrofisiologici.<\/p>\n\n\n\n<p>Abbiamo anche ridotto MeCP2 utilizzando una strategia con oligonucleotidi antisenso, che ha un maggiore potenziale traslazionale.<\/p>\n\n\n\n<p>Gli oligonucleotidi antisenso sono piccoli acidi nucleici modificati che possono ibridarsi selettivamente con l'RNA messaggero trascritto da un gene bersaglio e silenziarlo, e sono stati utilizzati con successo per correggere i deficit in diversi modelli murini.<\/p>\n\n\n\n<p>Abbiamo scoperto che il trattamento con oligonucleotidi antisenso induce un ampio salvataggio fenotipico in topi adulti sintomatici con duplicazione di MECP2 (MECP2-TG) e corregge i livelli di MECP2 in cellule linfoblastoidi di pazienti con duplicazione di MECP2 in modo dose-dipendente.<\/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\">Alla pubblicazione<\/a><\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Prof. Huda Zoghbi et al (Baylor College of Medicine, Texas, USA) published an article in the journal Nature entitled \u00ab\u00a0Reversible phenotype in mice using gene rescue or antisense oligonucleotides\u00a0\u00bb. This [&hellip;]<\/p>","protected":false},"author":1,"featured_media":4838,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[88],"tags":[],"class_list":["post-9394","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications-en"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Reversal of phenotypes in MECP2 duplication mice - 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\/it\/inversione-dei-fenotipi-nei-topi-con-duplicazione-di-mecp2\/\" \/>\n<meta property=\"og:locale\" content=\"it_IT\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Reversal of phenotypes in MECP2 duplication mice - DupMECP2\" \/>\n<meta property=\"og:description\" content=\"Prof. Huda Zoghbi et al (Baylor College of Medicine, Texas, USA) published an article in the journal Nature entitled \u00ab\u00a0Reversible phenotype in mice using gene rescue or antisense oligonucleotides\u00a0\u00bb. This [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/dupmecp2.eu\/it\/inversione-dei-fenotipi-nei-topi-con-duplicazione-di-mecp2\/\" \/>\n<meta property=\"og:site_name\" content=\"DupMECP2\" \/>\n<meta property=\"article:published_time\" content=\"2022-06-14T18:42:45+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-11-04T20:53:13+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"900\" \/>\n\t<meta property=\"og:image:height\" content=\"600\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Caroline\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Scritto da\" \/>\n\t<meta name=\"twitter:data1\" content=\"Caroline\" \/>\n\t<meta name=\"twitter:label2\" content=\"Tempo di lettura stimato\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minuti\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/\"},\"author\":{\"name\":\"Caroline\",\"@id\":\"https:\/\/dupmecp2.eu\/#\/schema\/person\/b41e8cbba153cd974ee340386af279ee\"},\"headline\":\"Reversal of phenotypes in MECP2 duplication mice\",\"datePublished\":\"2022-06-14T18:42:45+00:00\",\"dateModified\":\"2024-11-04T20:53:13+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/\"},\"wordCount\":379,\"publisher\":{\"@id\":\"https:\/\/dupmecp2.eu\/#organization\"},\"image\":{\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg\",\"articleSection\":[\"Publications\"],\"inLanguage\":\"it-IT\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/\",\"url\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/\",\"name\":\"Reversal of phenotypes in MECP2 duplication mice - DupMECP2\",\"isPartOf\":{\"@id\":\"https:\/\/dupmecp2.eu\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg\",\"datePublished\":\"2022-06-14T18:42:45+00:00\",\"dateModified\":\"2024-11-04T20:53:13+00:00\",\"breadcrumb\":{\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#breadcrumb\"},\"inLanguage\":\"it-IT\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"it-IT\",\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#primaryimage\",\"url\":\"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg\",\"contentUrl\":\"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg\",\"width\":900,\"height\":600},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Accueil\",\"item\":\"https:\/\/dupmecp2.eu\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Publications\",\"item\":\"https:\/\/dupmecp2.eu\/category\/publications-en\/?lang=en\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Reversal of phenotypes in MECP2 duplication mice\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/dupmecp2.eu\/#website\",\"url\":\"https:\/\/dupmecp2.eu\/\",\"name\":\"DupMECP2\",\"description\":\"EU\",\"publisher\":{\"@id\":\"https:\/\/dupmecp2.eu\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/dupmecp2.eu\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"it-IT\"},{\"@type\":\"Organization\",\"@id\":\"https:\/\/dupmecp2.eu\/#organization\",\"name\":\"DupMECP2\",\"url\":\"https:\/\/dupmecp2.eu\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"it-IT\",\"@id\":\"https:\/\/dupmecp2.eu\/#\/schema\/logo\/image\/\",\"url\":\"\",\"contentUrl\":\"\",\"caption\":\"DupMECP2\"},\"image\":{\"@id\":\"https:\/\/dupmecp2.eu\/#\/schema\/logo\/image\/\"}},{\"@type\":\"Person\",\"@id\":\"https:\/\/dupmecp2.eu\/#\/schema\/person\/b41e8cbba153cd974ee340386af279ee\",\"name\":\"Caroline\",\"sameAs\":[\"https:\/\/dupmecp2.eu\"],\"url\":\"https:\/\/dupmecp2.eu\/it\/author\/417a2385dc37aa45\/\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Inversione dei fenotipi nei topi con duplicazione di MECP2 - DupMECP2","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/dupmecp2.eu\/it\/inversione-dei-fenotipi-nei-topi-con-duplicazione-di-mecp2\/","og_locale":"it_IT","og_type":"article","og_title":"Reversal of phenotypes in MECP2 duplication mice - DupMECP2","og_description":"Prof. Huda Zoghbi et al (Baylor College of Medicine, Texas, USA) published an article in the journal Nature entitled \u00ab\u00a0Reversible phenotype in mice using gene rescue or antisense oligonucleotides\u00a0\u00bb. This [&hellip;]","og_url":"https:\/\/dupmecp2.eu\/it\/inversione-dei-fenotipi-nei-topi-con-duplicazione-di-mecp2\/","og_site_name":"DupMECP2","article_published_time":"2022-06-14T18:42:45+00:00","article_modified_time":"2024-11-04T20:53:13+00:00","og_image":[{"width":900,"height":600,"url":"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg","type":"image\/jpeg"}],"author":"Caroline","twitter_card":"summary_large_image","twitter_misc":{"Scritto da":"Caroline","Tempo di lettura stimato":"2 minuti"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#article","isPartOf":{"@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/"},"author":{"name":"Caroline","@id":"https:\/\/dupmecp2.eu\/#\/schema\/person\/b41e8cbba153cd974ee340386af279ee"},"headline":"Reversal of phenotypes in MECP2 duplication mice","datePublished":"2022-06-14T18:42:45+00:00","dateModified":"2024-11-04T20:53:13+00:00","mainEntityOfPage":{"@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/"},"wordCount":379,"publisher":{"@id":"https:\/\/dupmecp2.eu\/#organization"},"image":{"@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#primaryimage"},"thumbnailUrl":"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg","articleSection":["Publications"],"inLanguage":"it-IT"},{"@type":"WebPage","@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/","url":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/","name":"Inversione dei fenotipi nei topi con duplicazione di MECP2 - DupMECP2","isPartOf":{"@id":"https:\/\/dupmecp2.eu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#primaryimage"},"image":{"@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#primaryimage"},"thumbnailUrl":"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg","datePublished":"2022-06-14T18:42:45+00:00","dateModified":"2024-11-04T20:53:13+00:00","breadcrumb":{"@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#breadcrumb"},"inLanguage":"it-IT","potentialAction":[{"@type":"ReadAction","target":["https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/"]}]},{"@type":"ImageObject","inLanguage":"it-IT","@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#primaryimage","url":"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg","contentUrl":"https:\/\/dupmecp2.eu\/wp-content\/uploads\/2022\/06\/Zoghbi-2015.jpg","width":900,"height":600},{"@type":"BreadcrumbList","@id":"https:\/\/dupmecp2.eu\/reversal-of-phenotypes-in-mecp2-duplication-mice\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Accueil","item":"https:\/\/dupmecp2.eu\/"},{"@type":"ListItem","position":2,"name":"Publications","item":"https:\/\/dupmecp2.eu\/category\/publications-en\/?lang=en"},{"@type":"ListItem","position":3,"name":"Reversal of phenotypes in MECP2 duplication mice"}]},{"@type":"WebSite","@id":"https:\/\/dupmecp2.eu\/#website","url":"https:\/\/dupmecp2.eu\/","name":"DupMECP2","description":"UE","publisher":{"@id":"https:\/\/dupmecp2.eu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/dupmecp2.eu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"it-IT"},{"@type":"Organization","@id":"https:\/\/dupmecp2.eu\/#organization","name":"DupMECP2","url":"https:\/\/dupmecp2.eu\/","logo":{"@type":"ImageObject","inLanguage":"it-IT","@id":"https:\/\/dupmecp2.eu\/#\/schema\/logo\/image\/","url":"","contentUrl":"","caption":"DupMECP2"},"image":{"@id":"https:\/\/dupmecp2.eu\/#\/schema\/logo\/image\/"}},{"@type":"Person","@id":"https:\/\/dupmecp2.eu\/#\/schema\/person\/b41e8cbba153cd974ee340386af279ee","name":"Caroline","sameAs":["https:\/\/dupmecp2.eu"],"url":"https:\/\/dupmecp2.eu\/it\/author\/417a2385dc37aa45\/"}]}},"_links":{"self":[{"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/posts\/9394","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/comments?post=9394"}],"version-history":[{"count":0,"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/posts\/9394\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/media\/4838"}],"wp:attachment":[{"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/media?parent=9394"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/categories?post=9394"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/dupmecp2.eu\/it\/wp-json\/wp\/v2\/tags?post=9394"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}