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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,2,25]]},"abstract":"<jats:p>\n                    Identification of repeat-associated non-AUG (RAN) translation in trinucleotide (CAG) repeat diseases has led to the emerging concept that CAG repeat diseases are caused by nonpolyglutamine products. Nonetheless, the in vivo contribution of RAN translation to the pathogenesis of CAG repeat diseases remains elusive. Via CRISPR\/Cas9-mediated genome editing, we established knock-in mouse models that harbor expanded CAG repeats in the mouse\n                    <jats:italic>huntingtin<\/jats:italic>\n                    gene to express RAN-translated products with or without polyglutamine peptides. We found that RAN translation is not detected in the knock-in mouse models when expanded CAG repeats are expressed at the endogenous level. Consistently, the expanded CAG repeats that cannot be translated into polyglutamine repeats do not yield the neuropathological and behavioral phenotypes that were found in knock-in mice expressing expanded polyglutamine repeats. Our findings suggest that RAN-translated products do not play a major role in the pathogenesis of CAG repeat diseases and underscore the importance in targeting polyglutamine repeats for therapeutics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1919197117","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T20:06:15Z","timestamp":1581019575000},"page":"4411-4417","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["Lack of RAN-mediated toxicity in Huntington\u2019s disease knock-in mice"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4925-8710","authenticated-orcid":false,"given":"Su","family":"Yang","sequence":"first","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;"},{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luoxiu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,2,6]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-pathmechdis-012418-012857","article-title":"Polyglutamine repeats in neurodegenerative diseases","volume":"14","author":"Lieberman A. 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