{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:05:09Z","timestamp":1790265909487,"version":"4.1.0"},"reference-count":129,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Centre for Mitochondrial Research","award":["203105\/Z\/16\/Z"],"award-info":[{"award-number":["203105\/Z\/16\/Z"]}]},{"name":"Wellcome Centre for Mitochondrial Research","award":["V4923"],"award-info":[{"award-number":["V4923"]}]},{"name":"Wellcome Centre for Mitochondrial Research","award":["ARUK-SRF2022A-006"],"award-info":[{"award-number":["ARUK-SRF2022A-006"]}]},{"name":"Ryan Stanford Appeal and Great Ormond Street Hospital Charity","award":["203105\/Z\/16\/Z"],"award-info":[{"award-number":["203105\/Z\/16\/Z"]}]},{"name":"Ryan Stanford Appeal and Great Ormond Street Hospital Charity","award":["V4923"],"award-info":[{"award-number":["V4923"]}]},{"name":"Ryan Stanford Appeal and Great Ormond Street Hospital Charity","award":["ARUK-SRF2022A-006"],"award-info":[{"award-number":["ARUK-SRF2022A-006"]}]},{"name":"Alzheimer\u2019s Research UK Senior Fellowship","award":["203105\/Z\/16\/Z"],"award-info":[{"award-number":["203105\/Z\/16\/Z"]}]},{"name":"Alzheimer\u2019s Research UK Senior Fellowship","award":["V4923"],"award-info":[{"award-number":["V4923"]}]},{"name":"Alzheimer\u2019s Research UK Senior Fellowship","award":["ARUK-SRF2022A-006"],"award-info":[{"award-number":["ARUK-SRF2022A-006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondrial diseases represent the most common inherited neurometabolic disorders, for which no effective therapy currently exists for most patients. The unmet clinical need requires a more comprehensive understanding of the disease mechanisms and the development of reliable and robust in vivo models that accurately recapitulate human disease. This review aims to summarise and discuss various mouse models harbouring transgenic impairments in genes that regulate mitochondrial function, specifically their neurological phenotype and neuropathological features. Ataxia secondary to cerebellar impairment is one of the most prevalent neurological features of mouse models of mitochondrial dysfunction, consistent with the observation that progressive cerebellar ataxia is a common neurological manifestation in patients with mitochondrial disease. The loss of Purkinje neurons is a shared neuropathological finding in human post-mortem tissues and numerous mouse models. However, none of the existing mouse models recapitulate other devastating neurological phenotypes, such as refractory focal seizures and stroke-like episodes seen in patients. Additionally, we discuss the roles of reactive astrogliosis and microglial reactivity, which may be driving the neuropathology in some of the mouse models of mitochondrial dysfunction, as well as mechanisms through which cellular death may occur, beyond apoptosis, in neurons undergoing mitochondrial bioenergy crisis.<\/jats:p>","DOI":"10.3390\/ijms24119698","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T10:08:41Z","timestamp":1685700521000},"page":"9698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology"],"prefix":"10.3390","volume":"24","author":[{"given":"Elizaveta A.","family":"Olkhova","sequence":"first","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8795-6977","authenticated-orcid":false,"given":"Laura A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e1inne S.","family":"Gorman","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4HH, UK"},{"name":"NIHR Newcastle Biomedical Research Centre, Biomedical Research Building, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Erskine","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"NIHR Newcastle Biomedical Research Centre, Biomedical Research Building, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-2034","authenticated-orcid":false,"given":"Yi Shiau","family":"Ng","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"},{"name":"NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4HH, UK"},{"name":"NIHR Newcastle Biomedical Research Centre, Biomedical Research Building, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/ana.24362","article-title":"Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease","volume":"77","author":"Gorman","year":"2015","journal-title":"Ann. 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