{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:17:31Z","timestamp":1783487851059,"version":"3.55.0"},"reference-count":100,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2013,7,31]],"date-time":"2013-07-31T00:00:00Z","timestamp":1375228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:p>This year (2013) marks the 20th anniversary of identification of the causal genetic mutation for Huntington's disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>), a landmark discovery that heralded study of the biological underpinnings of this most common dominantly inherited neurodegenerative disorder. Among the variety of model organisms used to study <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> pathogenesis, the mouse model is by far the most commonly used mammalian genetic model. Much of our current knowledge regarding mutant huntingtin (mHtt)\u2010induced disease pathogenesis in mammalian models has been obtained by studying transgenic mouse models expressing mHtt N\u2010terminal fragments, full\u2010length murine or human mHtt. In this review, we focus on recent progress in using novel <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> mouse models with targeted mHtt expression in specific brain cell types. These models help to address\u00a0the role of distinct neuronal and non\u2010neuronal cell types in eliciting cell\u2010autonomous or non\u2010cell\u2010autonomous disease processes in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>. We also describe several mHtt transgenic mouse models with targeted mutations in Htt <jats:italic>cis<\/jats:italic>\u2010domains to address specific pathogenic hypotheses, ranging from mHtt proteolysis to post\u2010translational modifications. These novel mouse genetic studies, through direct manipulations of the causal <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> gene, utilize a reductionist approach to systematically unravel the cellular and molecular pathways that are targeted by mHtt in disease pathogenesis, and to potentially identify novel targets for therapy.<\/jats:p>","DOI":"10.1111\/febs.12418","type":"journal-article","created":{"date-parts":[[2013,7,6]],"date-time":"2013-07-06T06:10:42Z","timestamp":1373091042000},"page":"4382-4394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Genetic manipulations of mutant huntingtin in mice: new insights into Huntington's disease pathogenesis"],"prefix":"10.1111","volume":"280","author":[{"given":"C. Y. 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