Mitochondria possess their own DNA (mtDNA), which plays important roles in cellular respiration and energy consumption. Mutations in mtDNA can lead to severe human diseases. To advance our understanding of mitochondrial genetic disorders, there is a need to develop suitable animal models with targeted mtDNA mutations.
While previous attempts have been made, in-depth phenotypic changes resulting from mitochondrial gene knockout, i.e., the alterations in observable characteristics when a specific gene is inactivated, remain largely undocumented.
To address this, researchers from Korea used a programmable DNA base editing technology to analyze the genotypic and phenotypic impacts of knocking out the ND5 mitochondrial gene. This study, led by Dr. Hyunji Lee, Associate Professor in the Department of Biomedical Sciences at Korea University College of Medicine, Republic of Korea, created a nonsense mutation by changing a single nucleotide, introducing a premature stop codon in mice.
This mutation interrupts protein synthesis , generating a truncated, often nonfunctional protein and effectively causing a loss of function. Their study appeared online on November 1, 2024 in the journal Experimental & Molecular Medicine . Highlighting the significance of this achievement, senior author Prof.
Lee explains, "The mtDNA is difficult to access by editing tools like Cas9, limiting the studies on mitochondrial genetic disorders. Therefore, we employed the DddA-derived cytosine base editor (DdC.