@article{1fad35fbf89f4ec8b03f69302fa78c11,
title = "Loss of SLC25A46 causes neurodegeneration by affecting mitochondrial dynamics and energy production in mice",
abstract = "Recently, we identified biallelic mutations of SLC25A46 in patients withmultiple neuropathies. Functional studies revealed that SLC25A46may play an important role in mitochondrial dynamics bymediating mitochondrial fission. However, the cellular basis and pathogenic mechanismof the SLC25A46-related neuropathies are not fully understood. Thus, we generated a Slc25a46 knock-outmouse model. Mice lacking SLC25A46 displayed severe ataxia, mainly caused by degeneration of Purkinje cells. Increased numbers of small, unmyelinated and degenerated optic nerves as well as loss of retinal ganglion cells indicated optic atrophy. Compound muscle action potentials in peripheral nerves showed peripheral neuropathy associated with degeneration and demyelination in axons. Mutant cerebellar neurons have largemitochondria, which exhibit abnormal distribution and transport. Biochemically mutant mice showed impaired electron transport chain activity and accumulated autophagymarkers. Our results suggest that loss of SLC25A46 causes degeneration in neurons by affectingmitochondrial dynamics and energy production.",
author = "Zhuo Li and Yanyan Peng and Hufnagel, {Robert B.} and Hu, {Yueh Chiang} and Chuntao Zhao and Queme, {Luis F.} and Zaza Khuchua and Driver, {Ashley M.} and Fei Dong and {Richard Lu}, Q. and Lindquist, {Diana M.} and Jankowski, {Michael P.} and Stottmann, {Rolf W.} and Kao, {Winston W.Y.} and Taosheng Huang",
note = "Funding Information: We thank Dr. Yin Sun and Dr. Benjamin Liou (Cincinnati Children's Hospital) for sharing reagents and stimulating discussion on the degeneration analysis. We thank Geogianne M. Ciraolo and Tilat Rizvi (Cincinnati Children's Hospital) for help with electron microscopy. We thank Dr. Desheng Liang and Dr. Lingqian Wu (Central South University, China) for advice on progress of CMT-related genetics study. We thank the Transgenic Animal and Genome Editing Core at Cincinnati Children's Hospital for mouse production. This work was supported by the Center for Pediatric Genomics (CpG) Grant from the Cincinnati Children's Hospital and National Institute of Health (1R01EY026609-01) to TH. The EMG recordings were partially supported by National Institute of Health (R01AR064551-01A1) to MPJ. ZL is the recipient of an abroad grant from the Office of China Postdoctoral Council. Publisher Copyright: {\textcopyright} The Author 2017. Published by Oxford University Press. All rights reserved.",
year = "2017",
month = oct,
day = "1",
doi = "10.1093/hmg/ddx262",
language = "English (US)",
volume = "26",
pages = "3776--3791",
journal = "Human molecular genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "19",
}