{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:36:04Z","timestamp":1791210964312,"version":"4.1.0"},"reference-count":48,"publisher":"Society for Neuroscience","issue":"34","license":[{"start":{"date-parts":[[2008,2,22]],"date-time":"2008-02-22T00:00:00Z","timestamp":1203638400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,8,22]]},"abstract":"<jats:p>Several murine genetic models of Huntington's disease (HD) have been developed. Murine genetic models are crucial for identifying mechanisms of neurodegeneration in HD and for preclinical evaluation of possible therapies for HD. Longitudinal analysis of mutant phenotypes is necessary to validate models and to identify appropriate periods for analysis of early events in the pathogenesis of neurodegeneration. Here we report longitudinal characterization of the murine<jats:italic>Hdh<\/jats:italic><jats:sup>(CAG)150<\/jats:sup>knock-in model of HD. A series of behavioral tests at five different time points (20, 40, 50, 70, and 100 weeks) demonstrates an age-dependent, late-onset behavioral phenotype with significant motor abnormalities at 70 and 100 weeks of age. Pathological analysis demonstrated loss of striatal dopamine D<jats:sub>1<\/jats:sub>and D<jats:sub>2<\/jats:sub>receptor binding sites at 70 and 100 weeks of age, and stereological analysis showed significant loss of striatal neuron number at 100 weeks. Late-onset behavioral abnormalities, decrease in striatal dopamine receptors, and diminished striatal neuron number observed in this mouse model recapitulate key features of HD. The<jats:italic>Hdh<\/jats:italic><jats:sup>(CAG)150<\/jats:sup>knock-in mouse is a valid model to evaluate early events in the pathogenesis of neurodegeneration in HD.<\/jats:p>","DOI":"10.1523\/jneurosci.1830-07.2007","type":"journal-article","created":{"date-parts":[[2007,8,22]],"date-time":"2007-08-22T16:23:49Z","timestamp":1187799829000},"page":"8989-8998","source":"Crossref","is-referenced-by-count":129,"title":["Longitudinal Evaluation of the<i>Hdh<\/i><sup>(CAG)150<\/sup>Knock-In Murine Model of Huntington's Disease"],"prefix":"10.1523","volume":"27","author":[{"given":"Mary Y.","family":"Heng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara J.","family":"Tallaksen-Greene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Detloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger L.","family":"Albin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,8,22]]},"reference":[{"key":"2023041303270358000_27.34.8989.1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1212\/01.WNL.0000132965.14653.D1","article-title":"Onset and rate of striatal atrophy in preclinical Huntington disease","volume":"63","author":"Aylward","year":"2004","journal-title":"Neurology"},{"key":"2023041303270358000_27.34.8989.2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.12.2207"},{"key":"2023041303270358000_27.34.8989.3","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1212\/WNL.54.9.1753","article-title":"Decreased striatal monoaminergic terminals in Huntington disease","volume":"54","author":"Bohnen","year":"2000","journal-title":"Neurology"},{"key":"2023041303270358000_27.34.8989.4","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1523\/JNEUROSCI.19-08-03248.1999","article-title":"Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation","volume":"19","author":"Carter","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303270358000_27.34.8989.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6480"},{"key":"2023041303270358000_27.34.8989.6","doi-asserted-by":"crossref","unstructured":"Crawley JN (2000) What's wrong with my mouse? Behavioral phenotyping of transgenic and knockout mice. (Wiley, New York).","DOI":"10.1201\/9780849333644.pt3"},{"key":"2023041303270358000_27.34.8989.7","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.6.909"},{"key":"2023041303270358000_27.34.8989.8","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.3.503"},{"key":"2023041303270358000_27.34.8989.9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03979.x"},{"key":"2023041303270358000_27.34.8989.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.01.024"},{"key":"2023041303270358000_27.34.8989.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80764-3"},{"key":"2023041303270358000_27.34.8989.12","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"2023041303270358000_27.34.8989.13","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2337\/diabetes.48.3.649","article-title":"Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes","volume":"48","author":"Hurlbert","year":"1999","journal-title":"Diabetes"},{"key":"2023041303270358000_27.34.8989.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.01.029"},{"key":"2023041303270358000_27.34.8989.15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm133"},{"key":"2023041303270358000_27.34.8989.16","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360318"},{"key":"2023041303270358000_27.34.8989.17","doi-asserted-by":"publisher","DOI":"10.1038\/352077a0"},{"key":"2023041303270358000_27.34.8989.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2003.08.006"},{"key":"2023041303270358000_27.34.8989.19","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.2.137"},{"key":"2023041303270358000_27.34.8989.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"2023041303270358000_27.34.8989.21","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10295"},{"key":"2023041303270358000_27.34.8989.22","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10776"},{"key":"2023041303270358000_27.34.8989.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.09.016"},{"key":"2023041303270358000_27.34.8989.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(98)00016-5"},{"key":"2023041303270358000_27.34.8989.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.03895.x"},{"key":"2023041303270358000_27.34.8989.26","doi-asserted-by":"publisher","DOI":"10.1101\/gad.888401"},{"key":"2023041303270358000_27.34.8989.27","unstructured":"Paxinos G Franklin KBJ (2001) The mouse brain in stereotaxic coordinates (Academic, San Diego), Ed 2."},{"key":"2023041303270358000_27.34.8989.28","first-page":"5","article-title":"Cognitive and motor function in transgenic mice carrying excess copies of the 695 and 751 amino acid isoforms of the amyloid precursor protein gene","volume":"1","author":"Perry","year":"1995","journal-title":"Alzheimer's Res"},{"key":"2023041303270358000_27.34.8989.29","doi-asserted-by":"publisher","DOI":"10.1038\/2510"},{"key":"2023041303270358000_27.34.8989.30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.15.5733"},{"key":"2023041303270358000_27.34.8989.31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03783.x"},{"key":"2023041303270358000_27.34.8989.32","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.5.695"},{"key":"2023041303270358000_27.34.8989.33","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1212\/01.WNL.0000065888.88988.6E","article-title":"Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis","volume":"60","author":"Rosas","year":"2004","journal-title":"Neurology"},{"key":"2023041303270358000_27.34.8989.34","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000174432.87383.87"},{"key":"2023041303270358000_27.34.8989.35","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.3.397"},{"key":"2023041303270358000_27.34.8989.36","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.5.763"},{"key":"2023041303270358000_27.34.8989.37","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg169"},{"key":"2023041303270358000_27.34.8989.38","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.60.3.354-a"},{"key":"2023041303270358000_27.34.8989.39","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg077"},{"key":"2023041303270358000_27.34.8989.40","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20680"},{"key":"2023041303270358000_27.34.8989.41","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10855"},{"key":"2023041303270358000_27.34.8989.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.10.037"},{"key":"2023041303270358000_27.34.8989.43","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000176071.08694.cc"},{"key":"2023041303270358000_27.34.8989.44","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.nbd.2006.12.010","article-title":"Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain","volume":"1","author":"Van Raamsdonk","year":"2007","journal-title":"Neurobiol Dis 26"},{"key":"2023041303270358000_27.34.8989.45","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00001"},{"key":"2023041303270358000_27.34.8989.46","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400110"},{"key":"2023041303270358000_27.34.8989.47","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.4.503"},{"key":"2023041303270358000_27.34.8989.48","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1523\/JNEUROSCI.23-06-02193.2003","article-title":"Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease","volume":"23","author":"Yu","year":"2003","journal-title":"J Neurosci"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1830-07.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T18:11:52Z","timestamp":1681409512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.1830-07.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8,22]]},"references-count":48,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2007,8,22]]},"published-print":{"date-parts":[[2007,8,22]]}},"alternative-id":["10.1523\/JNEUROSCI.1830-07.2007"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.1830-07.2007","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8,22]]}}}