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Hallmarks of HD include brain volume loss and abnormal metabolism. However, HD is a multi-system disorder, and the impact on other organ systems is poorly understood. Using high-frequency ultrasound and nuclear magnetic resonance, we studied cardiac function (n=9-11 mice\/genotype\/sex) and brain metabolism (n=10 mice\/genotype\/sex) in a humanized transgenic mouse model of HD (Hu97\/18 mice) at 12\u2005months of age. The assessments were conducted in different cohorts and analyzed separately. Compared to controls (Hu18\/18 mice), Hu97\/18 mice showed a decrease in the left ventricle ejection fraction in both sexes and an increase in the E\/A ratio (E wave\/A wave diastolic filling) in females, indicative of mild cardiac dysfunction. The relative concentrations of several metabolites in the brain were altered in Hu97\/18 mice, compared to those in Hu18\/18 mice, and depended on sex and brain region. These findings are consistent with clinical features observed in human HD, supporting use of the Hu97\/18 model for investigation of pathophysiology in HD in multiple organ systems. It also highlights the importance of studying both sexes in HD research.<\/jats:p>","DOI":"10.1242\/dmm.052922","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:08:37Z","timestamp":1790755717000},"source":"Crossref","is-referenced-by-count":0,"title":["Sex-dependent mild cardiac dysfunction and neurometabolic abnormalities in a model of Huntington's disease"],"prefix":"10.1242","volume":"19","author":[{"given":"Kenna L. R.","family":"Hynes","sequence":"first","affiliation":[{"name":"Memorial University of Newfoundland 1 Department of Chemistry , , St John's, NL A1C 5S7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Memorial University of Newfoundland 1 Department of Chemistry , , St John's, NL A1C 5S7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Hanrahan","sequence":"additional","affiliation":[{"name":"Memorial University of Newfoundland 1 Department of Chemistry , , St John's, NL A1C 5S7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Neita","sequence":"additional","affiliation":[{"name":"Memorial University of Newfoundland 1 Department of Chemistry , , St John's, NL A1C 5S7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Nadine","family":"Burry","sequence":"additional","affiliation":[{"name":"Memorial University of Newfoundland 1 Department of Chemistry , , St John's, NL A1C 5S7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Hayden","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics 2 , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"BC Children's Hospital Research Institute 3 , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"University of British Columbia 4 Department of Medical Genetics , , Vancouver, BC V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Memorial University of Newfoundland 5 Faculty of Medicine, Division of Biomedical Sciences , , St John's, NL A1B 3X7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber L.","family":"Southwell","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, University of Central Florida 6 , Orlando, FL 32827 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1667-8564","authenticated-orcid":false,"given":"Lindsay S.","family":"Cahill","sequence":"additional","affiliation":[{"name":"Memorial University of Newfoundland 1 Department of Chemistry , , St John's, NL A1C 5S7 ,","place":["Canada"]},{"name":"Memorial University of Newfoundland 7 Division of Radiology , , St John's, NL A1B 3X7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"2026101406313949200_DMM052922C1","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1038\/s41467-022-29006-z","article-title":"DIAMetAlyzer allows automated false-discovery rate-controlled analysis for data-independent acquisition in metabolomics","volume":"13","author":"Alka","year":"2022","journal-title":"Nat. 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