{"id":15103,"date":"2022-06-14T20:42:45","date_gmt":"2022-06-14T18:42:45","guid":{"rendered":"https:\/\/dupmecp2.eu\/reversion-de-fenotipos-en-ratones\/"},"modified":"2023-02-20T20:06:52","modified_gmt":"2023-02-20T20:06:52","slug":"%ce%b1%ce%bd%ce%b1%cf%83%cf%84%cf%81%ce%bf%cf%86%ce%ae-%cf%84%cf%89%ce%bd-%cf%86%ce%b5%ce%bd%cf%8c%cf%84%ce%b9%cf%80%cf%89%ce%bd-%cf%83%ce%b5-%ce%b1%cf%81%ce%bf%cf%85%cf%81%ce%b1%ce%af%ce%bf%cf%85","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/el\/%ce%b1%ce%bd%ce%b1%cf%83%cf%84%cf%81%ce%bf%cf%86%ce%ae-%cf%84%cf%89%ce%bd-%cf%86%ce%b5%ce%bd%cf%8c%cf%84%ce%b9%cf%80%cf%89%ce%bd-%cf%83%ce%b5-%ce%b1%cf%81%ce%bf%cf%85%cf%81%ce%b1%ce%af%ce%bf%cf%85\/","title":{"rendered":"\u0391\u03bd\u03b1\u03c3\u03c4\u03c1\u03bf\u03c6\u03ae \u03c4\u03c9\u03bd \u03c6\u03b5\u03bd\u03cc\u03c4\u03b9\u03c0\u03c9\u03bd \u03c3\u03b5 \u03b1\u03c1\u03bf\u03c5\u03c1\u03b1\u03af\u03bf\u03c5\u03c2"},"content":{"rendered":"<p><strong>\u039f \u03ba\u03b1\u03b8\u03b7\u03b3\u03b7\u03c4\u03ae\u03c2 Huda Zoghbi \u03ba.\u03ac. (Baylor College of Medicine, \u03a4\u03ad\u03be\u03b1\u03c2, \u0397\u03a0\u0391) \u03b4\u03b7\u03bc\u03bf\u03c3\u03af\u03b5\u03c5\u03c3\u03b1\u03bd \u03ac\u03c1\u03b8\u03c1\u03bf \u03c3\u03c4\u03bf \u03c0\u03b5\u03c1\u03b9\u03bf\u03b4\u03b9\u03ba\u03cc Nature \u03bc\u03b5 \u03c4\u03af\u03c4\u03bb\u03bf \"Reversible phenotype in mice using gene rescue or antisense oligonucleotides\". Este art\u00edculo presenta los resultados del uso de oligonucle\u00f3tidos antisentido para corregir los niveles de MeCP2 y revertir los trastornos conductuales, moleculares y electrofisiol\u00f3gicos en un modelo animal con una duplicaci\u00f3n del gen MECP2.<\/strong><\/p>\n\n<p>\u0391\u03bd\u03c4\u03b9\u03c3\u03c4\u03c1\u03bf\u03c6\u03ae \u03c4\u03c9\u03bd \u03c6\u03b1\u03b9\u03bd\u03bf\u03c4\u03cd\u03c0\u03c9\u03bd \u03c3\u03b5 \u03c0\u03bf\u03bd\u03c4\u03af\u03ba\u03b9\u03b1 \u03bc\u03b5 \u03b4\u03b9\u03c0\u03bb\u03b1\u03c3\u03b9\u03b1\u03c3\u03bc\u03cc \u03c4\u03bf\u03c5 MECP2 \u03bc\u03b5 \u03c4\u03b7 \u03c7\u03c1\u03ae\u03c3\u03b7 \u03b3\u03b5\u03bd\u03b5\u03c4\u03b9\u03ba\u03ae\u03c2 \u03b4\u03b9\u03ac\u03c3\u03c9\u03c3\u03b7\u03c2 \u03ae \u03b1\u03bd\u03c4\u03b9\u03c3\u03b7\u03bc\u03b9\u03ba\u03ce\u03bd \u03bf\u03bb\u03b9\u03b3\u03bf\u03bd\u03bf\u03c5\u03ba\u03bb\u03b5\u03bf\u03c4\u03b9\u03b4\u03af\u03c9\u03bd, Huda Zoghbi <em>et al,<\/em> <em>\u03a6\u03cd\u03c3\u03b7<\/em><strong> 528, <\/strong>123-126 (2015)<\/p>\n\n<p><\/p>\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n<p><\/p>\n\n<p><strong>RESUMEN DE LA PUBLICACI\u00d3N:<\/strong><\/p>\n\n<p>\u0394\u03b9\u03b1\u03c6\u03bf\u03c1\u03bf\u03c0\u03bf\u03b9\u03ae\u03c3\u03b5\u03b9\u03c2 \u03c3\u03c4\u03bf\u03bd \u03b1\u03c1\u03b9\u03b8\u03bc\u03cc \u03c4\u03c9\u03bd \u03b1\u03bd\u03c4\u03b9\u03b3\u03c1\u03ac\u03c6\u03c9\u03bd \u03ad\u03c7\u03bf\u03c5\u03bd \u03c3\u03c5\u03c7\u03bd\u03ac \u03c3\u03c5\u03c3\u03c7\u03b5\u03c4\u03b9\u03c3\u03c4\u03b5\u03af \u03bc\u03b5 \u03b1\u03bd\u03b1\u03c0\u03c4\u03c5\u03be\u03b9\u03b1\u03ba\u03ae \u03ba\u03b1\u03b8\u03c5\u03c3\u03c4\u03ad\u03c1\u03b7\u03c3\u03b7, \u03b4\u03b9\u03b1\u03bd\u03bf\u03b7\u03c4\u03b9\u03ba\u03ae \u03b1\u03bd\u03b1\u03c0\u03b7\u03c1\u03af\u03b1 \u03ba\u03b1\u03b9 \u03b4\u03b9\u03b1\u03c4\u03b1\u03c1\u03b1\u03c7\u03ad\u03c2 \u03c4\u03bf\u03c5 \u03b1\u03c5\u03c4\u03b9\u03c3\u03c4\u03b9\u03ba\u03bf\u03cd \u03c6\u03ac\u03c3\u03bc\u03b1\u03c4\u03bf\u03c2. El s\u00edndrome de duplicaci\u00f3n del MECP2 es uno de los m\u00e1s reordenamientos gen\u00f3micos comunes en varones y se caracteriza por autismo, discapacidad intelectual, disfunci\u00f3n motora, ansiedad, epilepsia, infecciones recurrentes de las v\u00edas respiratorias y muerte prematura.<\/p>\n\n<p>La amplia gama de d\u00e9ficits causados por la sobreexpresi\u00f3n de la prote\u00edna de uni\u00f3n a metil-CpG 2 (MeCP2) plantea un reto de enormes proporciones a los tratamientos terap\u00e9uticos tradicionales basados en v\u00edas bioqu\u00edmicas. En consecuencia, buscamos estrategias que se dirijan directamente al MeCP2 y que sean susceptibles de traducirse en terapia cl\u00ednica.<\/p>\n\n<p>La primera cuesti\u00f3n en la que nosotros nos enfocamos fue si la disfunci\u00f3n neurol\u00f3gica es reversible tras la aparici\u00f3n de los s\u00edntomas. La reversi\u00f3n de los fenotipos en ratones adultos sintom\u00e1ticos han demostrado en algunos modelos de p\u00e9rdida monog\u00e9nica funcional en trastornos neurol\u00f3gicos, incluyendo la p\u00e9rdida de MeCP2 en el s\u00edndrome de Rett. lo que indica, que al menos en algunos casos, la neuroanatom\u00eda puede permanecer suficientementemente intacta de modo que la correcci\u00f3n de la disfunci\u00f3n molecular subyacente a estos trastornos pueda restaurar la fisiolog\u00eda saludable.<\/p>\n\n<p>Dada la ausencia de neurodegeneraci\u00f3n en el s\u00edndrome de duplicaci\u00f3n MECP2, proponemos que la restauraci\u00f3n de los niveles normales de MeCP2 en ratones adultos con duplicaci\u00f3n MECP2 rescatar\u00eda su fenotipo.<\/p>\n\n<p>Mediante la generaci\u00f3n y caracterizaci\u00f3n de un modelo de sobreexpresi\u00f3n condicional de MeCP2 en ratones, demostramos que la correcci\u00f3n MeCP2 revierte en gran medida los d\u00e9ficits conductuales, moleculares y electrofisiol\u00f3gicos.<\/p>\n\n<p>Tambi\u00e9n redujimos MeCP2 mediante una estrategia de oligonucle\u00f3tidos antisentido que tiene un mayor potencial translacional.<\/p>\n\n<p>Los oligonucle\u00f3tidos antisentido son peque\u00f1os \u00e1cidos nucleicos modificados que pueden hibridarse selectiveamente con el ARN mensajero transcrito de un gen blanco y silenciarlo, dicha t\u00e9cnica ha sido usada exitosamente para corregir d\u00e9ficits en diferentes modelos en ratones.<\/p>\n\n<p>Hemos descubierto que el tratamiento con los oligonucle\u00f3tidos antisentido induce un amplio rescate fenot\u00edpico en ratones transg\u00e9nicos adultos sintom\u00e1ticos con duplicaci\u00f3n MECP2 (MECP2-TG) y corrige los niveles de MeCP2 en c\u00e9lulas linfoblastoides de pacientes con duplicaci\u00f3n MECP2 de forma dosis-dependiente.<\/p>\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n<p><\/p>\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\">Ver la publicaci\u00f3n<\/a><\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Prof. Huda Zoghbi et al (Baylor College of Medicine, Texas, EE.UU.) publicaron un art\u00edculo en la revista Nature titulado \u00ab\u00a0Reversible phenotype in mice using gene rescue or antisense oligonucleotides\u00a0\u00bb. Este [&hellip;]<\/p>","protected":false},"author":1,"featured_media":13096,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[113],"tags":[],"class_list":["post-15103","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publicacion"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Reversi\u00f3n de fenotipos en ratones - 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\/\u03b1\u03bd\u03b1\u03c3\u03c4\u03c1\u03bf\u03c6\u03ae-\u03c4\u03c9\u03bd-\u03c6\u03b5\u03bd\u03cc\u03c4\u03b9\u03c0\u03c9\u03bd-\u03c3\u03b5-\u03b1\u03c1\u03bf\u03c5\u03c1\u03b1\u03af\u03bf\u03c5\/?lang=es\" \/>\n<meta property=\"og:locale\" content=\"el_GR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Reversi\u00f3n de fenotipos en ratones - DupMECP2\" \/>\n<meta property=\"og:description\" content=\"Prof. Huda Zoghbi et al (Baylor College of Medicine, Texas, EE.UU.) publicaron un art\u00edculo en la revista Nature titulado \u00ab\u00a0Reversible phenotype in mice using gene rescue or antisense oligonucleotides\u00a0\u00bb. 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