A Novel ENU-Induced Mfn2 Mutation Causes Motor Deficits in Mice without Causing Peripheral Neuropathy

Mitochondrial fission and fusion are required for maintaining functional mitochondria. The mitofusins (MFN1 MFN2) known their roles in mediating mitochondrial fusion. Recently, MFN2 has been implicated other important cellular functions, such as mitophagy, motility, coordinating endoplasmic reticulum-mitochondria communication. In humans, over 100 mutations associated with a form of inherited peripheral neuropathy, Charcot–Marie–Tooth disease type 2A (CMT2A). Here we describe an ENU-induced mutant mouse line recessive neuromuscular phenotype. Behavioral screening showed progressive weight loss rapid deterioration motor function beginning at 8 weeks. Mapping sequencing revealed missense mutation exon 18 Mfn2 (T1928C; Leu643Pro), within the transmembrane domain. Compared to wild-type heterozygous littermates, Mfn2L643P/L643P mice exhibited diminished rotarod performance decreases activity open field test, muscular endurance, mean diameter, sensory tests, DNA content, protein levels. However, tests nerve physiology histology were largely normal. Mutant leg bones had reduced cortical bone thickness area fraction. Together, our data indicate that Mfn2L643P causes phenotype mild defects mice. Lack apparent pathology notwithstanding, this is first reported model domain protein, which may be valuable researchers studying biology.