phenotypic assessment of mtND5 nonsense mutation mice

Mitochondrial dysfunction induced by mitochondrial DNA (mtDNA) mutations has been implicated in various human diseases. A comprehensive analysis of mitochondrial genetic disorders requires suitable animal models for human disease studies. While gene knockout via premature stop codon is a powerful method for investigating unique functions of target genes, achieving knockout of mtDNA has been rare. Here we report genotypes and phenotypes of heteroplasmic MT-ND5 gene-knockout mice. These mutant mice exhibited damaged mitochondrial cristae in the cerebral cortex, hippocampal atrophy and asymmetry, leading to learning and memory abnormalities. Moreover, mutant mice were susceptible to obesity and thermogenetic disorder. We propose that these mtDNA gene-knockdown mice could serve as a valuable animal model for studying the MT-ND5 gene and developing therapies for human mitochondrial disorders in the future