{"id":7365,"date":"2022-06-14T20:42:45","date_gmt":"2022-06-14T20:42:45","guid":{"rendered":"http:\/\/carola.wwwnl1-sr12.supercp.com\/2022\/06\/14\/reversibler-phaenotyp-bei-humanisierten-maeusen\/"},"modified":"2023-01-13T11:46:50","modified_gmt":"2023-01-13T11:46:50","slug":"reversibler-phaenotyp-bei-humanisierten-maeusen","status":"publish","type":"post","link":"https:\/\/dupmecp2.eu\/pl\/reversibler-phaenotyp-bei-humanisierten-maeusen\/","title":{"rendered":"Reversibler Ph\u00e4notyp bei humanisierten M\u00e4usen"},"content":{"rendered":"<p><strong>Shao i wsp. z grupy prof. Zoghbi (Baylor College of Medicine, Teksas, USA) opublikowali w czasopi\u015bmie Science Translational medicine artyku\u0142 zatytu\u0142owany \"Antisense-Oligonucleotid-Therapie auf einem humanisierten Mausmodell des MECP2-Duplikation Syndroms\". <\/strong><\/p>\n\n\n\n<p><strong>Ka\u017cdy gatunek posiada geny, kt\u00f3re s\u0105 dla niego charakterystyczne. Gen koduje bia\u0142ka, kt\u00f3re s\u0105 specyficzne dla ka\u017cdego gatunku. Dlatego mo\u017cliwe jest rozr\u00f3\u017cnienie mi\u0119dzy bia\u0142kami ludzkimi i zwierz\u0119cymi. Das in der vorliegenden Studie verwendete Modell, das als \"humanisiertes Modell\" bezeichnet wird, erm\u00f6glicht es, die Aktivit\u00e4t von Antisense-Oligonukleotiden (ASOs) spezifisch auf humanes Protein, das von einer Maus produziert wird, besser zu bewerten. Dlatego tak wa\u017cne jest przysz\u0142e zastosowanie ASO u ludzi.<\/strong><\/p>\n\n\n\n<p><strong>In diesem Artikel werden die Ergebnisse vorgestellt, die nach intrazerebroventrikul\u00e4rer Injektion von Antisense-Oligonukleotiden in diesem \"humanisierten MECP2 gen-duplikation\"-Mausmodell beobachtet wurden, bei die Maus zwei menschliche MECP2-Alle und kein endogenes Maus-Alle tr\u00e4gt.<\/strong><\/p>\n\n\n\n<p><strong>Werbreichung w znacznym stopniu zmniejszy\u0142 ekspresj\u0119 MeCP2 w ca\u0142ym organizmie, z\u0142agodzi\u0142 inne zaburzenia wch\u0142aniania i zwi\u0119kszy\u0142 ekspresj\u0119 najsilniejszego genu reguluj\u0105cego MeCP2 dawkowanego bez \u017cadnej toksyczno\u015bci.<\/strong><\/p>\n\n\n\n<p>Terapia oligonukleotydami antysensownymi w humanizowanym mysim modelu zespo\u0142u duplikacji MECP2, Shao i in.<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>ZUSAMMENFASSUNG DES ARTIKELS (von Englisch \u00fcbersetzt):<\/strong><\/p>\n\n\n\n<p>Wiele stan\u00f3w chorobowych, kt\u00f3re prowadz\u0105 do powa\u017cnych zaburze\u0144 zachowania, jest spowodowanych zmianami kopalnianymi i do tej pory nie opracowano \u017cadnych opcji terapeutycznych dla tego typu schorze\u0144. Zesp\u00f3\u0142 duplikacji MECP2 jest jednym z najcz\u0119stszych zaburze\u0144 genomowych u m\u0119\u017cczyzn i wynika z duplikacji, kt\u00f3re wyst\u0119puj\u0105 w genotypie bia\u0142ka wi\u0105\u017c\u0105cego metylo-CpG 2 (MECP2). Wir haben zuvor gezeigt, dass die Therapie mit Antisense-Oligonukleotiden (ASO) die Menge des MECP2-Proteins in einem Mausmodell it MECP2 gen-duplikation reduzieren und die charakteristischen Symptome des Syndroms umkehren kann.<\/p>\n\n\n\n<p>Dieses Mausmodell mit MECP2-Genduplikation Syndrome 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>Bia\u0142ko MeCP2 jest bia\u0142kiem o wysokim st\u0119\u017ceniu. ASO powinno zatem by\u0107 w stanie twierdzi\u0107, \u017ce ilo\u015b\u0107 MeCP2 nie jest wyra\u017anie zmniejszona, bior\u0105c pod uwag\u0119, \u017ce powoduje to zesp\u00f3\u0142 Retta. Dlatego opracowali\u015bmy \"humanizowany model MECP2\" zespo\u0142u enduplikacji MECP2, w kt\u00f3rym Maus ma dwa m\u0119skie allele MECP2 i nie ma endogennych alleli Maus. Dzi\u0119ki \u015br\u00f3db\u0142onkowej iniekcji ASO-MECP2 ekspresja MeCP2 w ca\u0142ym organizmie m\u0119\u017cczyzny zosta\u0142a znacznie zmniejszona. Z drugiej strony, ASO-MECP2 z\u0142agodzi\u0142o wiele wad rozwojowych i zwi\u0119kszy\u0142o ekspresj\u0119 najlepszego genu reguluj\u0105cego MeCP2 w dawce i bez \u017cadnej toksyczno\u015bci. Weryfikacja ASO-MECP2 w centralnym uk\u0142adzie nerwowym jest zatem w tym modelu klinicznym bardzo wyra\u017ana i skuteczna oraz stanowi istotn\u0105 wskaz\u00f3wk\u0119 dla leczenia zespo\u0142u upo\u015bledzenia 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\"><a class=\"wp-block-button__link has-white-color has-text-color 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\">Publikation ansehen<\/a><\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Shao et al. aus der Gruppe von Prof. Zoghbi (Baylor College of Medicine, Texas, USA) publizieren in der Zeitschrift Science Translational medicine einen Artikel mit dem Titel \u00ab\u00a0Antisense-Oligonucleotid-Therapie auf einem [&hellip;]<\/p>","protected":false},"author":1,"featured_media":11724,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[58],"tags":[],"class_list":["post-7365","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publikationen"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - 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