{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:00:41Z","timestamp":1760853641016},"reference-count":65,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,6,25]],"date-time":"2012-06-25T00:00:00Z","timestamp":1340582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntington\u2019s disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the <jats:italic>huntingtin<\/jats:italic> (<jats:italic>htt<\/jats:italic>) gene. Neuropathology is most severe in the striatum and cerebral cortex. As mutant <jats:italic>htt<\/jats:italic> is ubiquitously expressed, it has not been possible to establish clear structure\u2010to\u2010function relationships for the clinical aspects. In the present study, we have injected recombinant adeno\u2010associated viral vectors of serotype 5 (rAAV5) expressing an 853\u2010amino\u2010acid fragment of htt with either 79 (mutant) or 18 (wild\u2010type) glutamines (Q) in the dorsal striatum of neonatal rats to achieve expression of <jats:italic>htt<\/jats:italic> in the forebrain. Rats were followed for 6\u2003months and compared with control rats. Neuropathological assessment showed long\u2010term expression of the green fluorescent protein (GFP) transgene (used as a marker protein) and accumulation of htt inclusions in the cerebral cortex with the rAAV5\u2010htt\u201079Q vectors. We estimated that around 10% of NeuN\u2010positive cells in the cerebral cortex and 2% of DARPP\u201032 neurons in the striatum were targeted with the GFP\u2010expressing vector. Formation of intracellular htt inclusions was not associated with neuronal loss, gliosis or microglia activation and did not lead to altered motor activity or changes in body weight. However, the same mutant <jats:italic>htt<\/jats:italic> vector caused orexin loss in the hypothalamus \u2013 another area known to be affected in HD. In conclusion, our results demonstrate that widespread forebrain expression of mutant <jats:italic>htt<\/jats:italic> can be achieved using rAAV5\u2010vectors and suggest that this technique can be further explored to study region\u2010specific effects of mutant <jats:italic>htt<\/jats:italic> or other disease\u2010causing genes in the brain.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2012.08193.x","type":"journal-article","created":{"date-parts":[[2012,6,26]],"date-time":"2012-06-26T13:11:34Z","timestamp":1340716294000},"page":"2789-2800","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Characterization of a rat model of Huntington\u2019s disease based on targeted expression of mutant <i>huntingtin<\/i> in the forebrain using adeno\u2010associated viral vectors"],"prefix":"10.1111","volume":"36","author":[{"given":"Sanaz","family":"Gabery","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad U.","family":"Sajjad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Hult","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rana","family":"Soylu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deniz","family":"Kirik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c5sa","family":"Peters\u00e9n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,6,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-09-03473.2002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02915-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn159"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.11.057"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn206"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70178-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-03-00961.2003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00169-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.128"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2010.07.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(93)90026-N"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1104"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1073\/pnas.97.7.3428","article-title":"Recombinant adeno\u2010associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system","volume":"97","author":"Davidson B.L.","year":"2000","journal-title":"Proc. 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