Comprehensive phenotypic assessment of nonsense mutations in mitochondrial ND5 in 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 codons is a powerful method for investigating the unique functions of target genes, achieving knockout of mtDNA has been rare. Here, we report the genotypes and phenotypes of heteroplasmic MT-ND5 gene-knockout mice. These mutant mice presented damaged mitochondrial cristae in the cerebral cortex, hippocampal atrophy, and asymmetry, leading to learning and memory abnormalities. Moreover, mutant mice are susceptible to obesity and thermogenetic disorders. We propose that these mtDNA gene-knockdown mice could serve as valuable animal models for studying the MT-ND5 gene and developing therapies for human mitochondrial disorders in the future. Mitochondria, often referred to as cell''s powerhouses, are essential for energy production and health. In this study, researchers used recently developed ways to edit mtDNA, allowing precise changes to study disease results in animal models. They performed an experiment involving the injection of specially designed mRNAs, into mouse embryos to cause specific changes in mtDNA. This method allowed the creation of mice with targeted mitochondrial gene removals, providing a useful model for studying mitochondrial diseases. Researchers found that mice with certain mtDNA changes showed symptoms like human mitochondrial diseases, such as brain abnormalities and metabolic issues. These findings emphasize the importance of mtDNA in health and disease, providing insights into how specific changes can affect bodily functions. Future research may use these findings to develop therapies targeting mtDNA changes. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.