Document Type

Article

Publication Date

7-3-2023

JAX Source

Biology (Basel). 2023;12(7):953.

ISSN

2079-7737

PMID

37508383

DOI

https://doi.org/10.3390/biology12070953

Grant

Development of the mice was supported by Novartis Grant SFP-1406. T.J.H. was supported by the 2021 Uplifting Athletes Young Investigator Draft and the Charcot-Marie-Tooth Association. A.R.G. was supported by NIGMS through P20GM121301, Phase I: Mesenchymal and Neural Regula- tion of Metabolic Networks, Lucy Liaw, PhD, Program Director and start up research funds from MHIR. L.M.T. was supported by with funding from the Genomics Institute of the Novartis Research Foundation (GNF). R.W.B. was supported by the National Institutes of Health (NIH) (R37 NS054154, R24 NS098523).

Abstract

The fission and fusion of mitochondria are important processes for maintaining mitochondrial health. One of the proteins responsible for mediating mitochondrial fusion, mitofusin 2 (MFN2), has over 100 known mutations that cause Charcot–Marie–Tooth disease type 2A (CMT2A). This disease causes the nerves that control your muscles to degenerate, leading to muscle atrophy and weakness, problems walking, and other related symptoms. In this paper, we describe a mouse line with a recessive mutation in the Mfn2 gene (Leu643Pro) that causes a similar set of symptoms, including abnormal gait, weight loss, and decreased muscular endurance. However, further analysis of these mice revealed signs of skeletal muscle dysfunction (including smaller mitochondria) and bone abnormalities, with little evidence of axon degeneration typical of CMT2A. While this makes these mice a poor model for CMT2A, they are the first reported mouse line with a mutation in the transmembrane domain, a region critical for MFN2′s role in mitochondrial fusion. For this reason, we believe these mice will be a valuable tool for scientists interested in studying the biological functions of MFN2.

Comments

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Download

Share

COinS