{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:04:32Z","timestamp":1789758272753,"version":"4.0.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Huntington disease (HD) is caused by the expansion of CAG triplet repeats in exon 1 of the <jats:italic>huntingtin (HTT)<\/jats:italic> gene, which also encodes the first 17 amino acids (N-17) that can modulate the toxicity of the expanded polyQ repeat. N-17 are conserved in a wide range of species and are found to influence the subcellular distribution of mutant Htt. Moreover, N-17 is subject to many posttranslational modifications that may regulate the function, stability, and distribution of HTT. However, the function of Htt exon 1 and its influence on the normal Htt remains to be fully investigated. By investigating a knock-in mouse model that lacks <jats:italic>Htt<\/jats:italic> exon1, we found that deletion of <jats:italic>Htt<\/jats:italic> exon1 does not affect the survival of mice and differentiation of cultured mouse neurons. Furthermore, the lack of <jats:italic>Htt<\/jats:italic> exon 1 does not alter the subcellular distribution of Htt, autophagy protein expression, and global gene transcription in the mouse brain. These results suggest that removing the entire exon 1 of Htt could be a therapeutic approach to eliminate expanded polyQ toxicity.<\/jats:p>","DOI":"10.3389\/fncel.2022.1021592","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T07:14:16Z","timestamp":1668064456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Huntingtin exon 1 deletion does not alter the subcellular distribution of huntingtin and gene transcription in mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Xianxian","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yize","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiqiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3233\/JHD-160231","article-title":"Generation and characterization of knock-in mouse models expressing versions of huntingtin with either an N17 or a combined PolyQ and proline-rich region deletion","volume":"6","author":"Andr\u00e9","year":"2017","journal-title":"J. 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