Kim Sanghun, Park Seul Gi, Kim Jieun, Hong Seongho, Cho Sang-Mi, Lim Soo-Yeon, Kim Eun-Kyoung, Ju Sungjin, Lee Su Bin, Kim Sol Pin, Jeong Tae Young, Oh Yeji, Han Seunghun, Kim Hae-Rim, Lee Taek Chang, Kim Hyoung-Chin, Yoon Won Kee, An Tae Hyeon, Oh Kyoung-Jin, Nam Ki-Hoan, Lee Seonghyun, Kim Kyoungmi, Seong Je Kyung, Lee Hyunji
Department of Biomedical Sciences, Korea University College of Medicine, Seoul, 02841, Republic of Korea.
Laboratory Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, 28116, Republic of Korea.
Exp Mol Med. 2024 Nov;56(11):2395-2408. doi: 10.1038/s12276-024-01333-9. Epub 2024 Nov 1.
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.
线粒体DNA（mtDNA）突变引起的线粒体功能障碍与多种人类疾病有关。对线粒体遗传疾病进行全面分析需要适用于人类疾病研究的动物模型。虽然通过提前终止密码子进行基因敲除是研究靶基因独特功能的有力方法，但实现mtDNA的敲除却很少见。在这里，我们报告了异质性MT-ND5基因敲除小鼠的基因型和表型。这些突变小鼠在大脑皮层出现线粒体嵴受损、海马萎缩和不对称，导致学习和记忆异常。此外，突变小鼠易患肥胖症和产热障碍。我们认为，这些mtDNA基因敲低小鼠可作为未来研究MT-ND5基因和开发人类线粒体疾病治疗方法的有价值的动物模型。
