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Exp. Mol. Med., 01 November 2024 | https://doi.org/10.1038/s12276-024-01333-9 Comprehensive phenotypic assessment of nonsense mutations in mitochondrial ND5 in mice

Sanghun Kim ^1,11, Seul Gi Park ^2,11, Jieun Kim ¹, Seongho Hong ^3,4, Sang-Mi Cho ², Soo-Yeon Lim ⁴, Eun-Kyoung Kim ², Sungjin Ju ^1,5, Su Bin Lee ⁴, Sol Pin Kim ^3,4, Tae Young Jeong ^1,5, Yeji Oh ¹, Seunghun Han ², Hae-Rim Kim ², Taek Chang Lee ², Hyoung-Chin Kim ², Won Kee Yoon ², Tae Hyeon An ^6,7, Kyoung-jin Oh ^6,7, Ki-Hoan Nam^2,*, Seonghyun Lee ^8,9,*, Kyoungmi Kim ^1,5,*, Je Kyung Seong ^3,4,* and Hyunji Lee ^1,2,10,*

¹Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea.
²Laboratory Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea.
³Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
⁴Korea Model animal Priority Center, Seoul National University, Seoul 08826, Republic of Korea.
⁵Department of Physiology, Korea University College of Medicine, Seoul 02841, Republic of Korea.
⁶Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
⁷Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34141, Republic of Korea.
⁸Department of MetaBioHealth, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.
⁹Department of Precision Medicine, School of Medicine, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.
¹⁰Department of Convergence Medicine, Korea University College of Medicine, Seoul 02708, Republic of Korea.
¹¹These authors contributed equally: Sanghun Kim, Seul Gi Park.

^*Corresponding authors: correspondence to Ki-Hoan Nam, Seonghyun Lee, Kyoungmi Kim, Je Kyung Seong or Hyunji Lee

Abstract

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.

논문정보

형식Research article
게재일2024년 11월 (BRIC 등록일 2024-11-01)
연구진국내 연구진
분야 의약학 > 유전 및 유전체의학

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