{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:59:36Z","timestamp":1790182776161,"version":"4.1.0"},"reference-count":55,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T00:00:00Z","timestamp":1474329600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Huntington's Disease"],"published-print":{"date-parts":[[2016,9,24]]},"abstract":"<jats:p>Background: Huntington\u2019s disease (HD) is caused by an unstable polyglutamine (CAG) repeat in the HD gene, whereby a CAG repeat length greater than \u223c36 leads to the disease. In HD patients, longer repeats correlate with more severe disease and earlier death. This is also seen in R6\/2 mice carrying repeat lengths up to \u223c200. Paradoxically, R6\/2 mice with repeat lengths &gt;300 have a less aggressive phenotype and longer lifespan than those with shorter repeats. The mechanism underlying this phenomenon is unknown.<\/jats:p>\n                  <jats:p>Objective: To investigate the consequences of longer repeat lengths on structural changes in the brains of R6\/2 mice, especially with regard to progressive atrophy.<\/jats:p>\n                  <jats:p>Methods: We used longitudinal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) to compare pathological changes in two strains of R6\/2 mice, one with a rapidly progressing disease (250 CAG repeats), and the other with a less aggressive phenotype (350 CAG repeats).<\/jats:p>\n                  <jats:p>Results: We found significant progressive brain atrophy in both 250 and 350 CAG repeat mice, as well as changes in metabolites (glutamine\/glutamate, choline and aspartate). Although similar in magnitude, atrophy in the brains of 350 CAG R6\/2 mice progressed more slowly than that seen in 250 CAG mice, in line with the milder phenotype and longer lifespan. Interestingly, significant atrophy was detectable in 350 CAG mice as early as 8\u201312 weeks of age, although behavioural abnormalities in these mice are not apparent before 25\u201330 weeks. This finding fits well with human data from the PREDICT-HD and TRACK-HD project, where reductions in brain volume were found 10 years in advance of the onset of symptoms.<\/jats:p>\n                  <jats:p>Conclusions: The similar brain atrophy with a mismatch between onset of brain atrophy and behavioural phenotype in HD mice with 350 repeats will make this mouse particularly useful for modelling early stages of HD pathology.<\/jats:p>","DOI":"10.3233\/jhd-160208","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T11:07:49Z","timestamp":1474369669000},"page":"271-283","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Similar Progression of Morphological and\u00a0Metabolic Phenotype in R6\/2 Mice with Different CAG Repeats Revealed by\n                    <i>In Vivo<\/i>\n                    Magnetic Resonance Imaging and Spectroscopy"],"prefix":"10.1177","volume":"5","author":[{"given":"Stephen J.","family":"Sawiak","sequence":"first","affiliation":[{"name":"Wolfson Brain Imaging Centre, University of Cambridge, Box 65 Addenbrooke\u2019s Hospital, Cambridge, UK"},{"name":"Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel I.","family":"Wood","sequence":"additional","affiliation":[{"name":"Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Jennifer","family":"Morton","sequence":"additional","affiliation":[{"name":"Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,9,20]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60111-1"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420411"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010887421592"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01884-8"},{"issue":"1","key":"ref005","first-page":"16","volume":"59","author":"Rubinsztein DC","year":"1996","journal-title":"Am J Hum 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