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Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology

Lookup NU author(s): Dr Elizaveta Olkhova, Laura Alexandra Smith, Carla Bradshaw, Professor Grainne Gorman, Dr Daniel ErskineORCiD, Dr Yi NgORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 by the authors. 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.

Publication metadata

Author(s): Olkhova EA, Smith LA, Bradshaw C, Gorman GS, Erskine D, Ng YS

Publication type: Review

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2023

Volume: 24

Issue: 11

Online publication date: 02/06/2023

Acceptance date: 29/05/2023

ISSN (print): 1661-6596

ISSN (electronic): 1422-0067

Publisher: MDPI


DOI: 10.3390/ijms24119698