Primate Model Carrying LMNA Mutation Develops Dilated Cardiomyopathy

Xiang Luo; Hao Jia; Fang Wang; Han Mo; Yu Kang; Ningning Zhang; Lu Zhao; Lizhu Xu; Zhengsheng Yang; Qiaoyan Yang; Yuan Chang; Shulin Li; Ning Bian; Xiumeng Hua; Hao Cui; Yu Cao; Chu Chu; Yuqiang Zeng; Xinglong Chen; Zhigang Chen; Weizhi Ji; Chengzu Long; Jiangping Song; Yuyu Niu

doi:10.1016/j.jacbts.2023.11.002

Primate Model Carrying LMNA Mutation Develops Dilated Cardiomyopathy

JACC Basic Transl Sci. 2024 Jan 24;9(3):380-395. doi: 10.1016/j.jacbts.2023.11.002. eCollection 2024 Mar.

Authors

Xiang Luo^{1

2

3}, Hao Jia⁴, Fang Wang^{1

2}, Han Mo^{4

5}, Yu Kang^{1

2}, Ningning Zhang⁴, Lu Zhao^{1

2}, Lizhu Xu¹, Zhengsheng Yang¹, Qiaoyan Yang⁶, Yuan Chang⁴, Shulin Li^{1

2}, Ning Bian^{1

2}, Xiumeng Hua⁴, Hao Cui⁴, Yu Cao^{7

8}, Chu Chu^{1

2}, Yuqiang Zeng^{1

2}, Xinglong Chen¹, Zhigang Chen¹, Weizhi Ji^{1

2}, Chengzu Long^{6

9

10}, Jiangping Song^{4

5}, Yuyu Niu^{1

2

3}

Affiliations

¹ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.
² Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, China.
³ Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
⁴ Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, National Centre for Cardiovascular Disease, Department of Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China.
⁶ NYU Cardiovascular Research Center, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York, USA.
⁷ Department of Cardiovascular Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
⁸ Yunnan Key Laboratory of Innovative Application of Traditional Chinese Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
⁹ Department of Neuroscience and Physiology, New York University School of Medicine, New York, New York, USA.
¹⁰ Department of Neurology, New York University School of Medicine, New York, New York, USA.

Abstract

To solve the clinical transformation dilemma of lamin A/C (LMNA)-mutated dilated cardiomyopathy (LMD), we developed an LMNA-mutated primate model based on the similarity between the phenotype of primates and humans. We screened out patients with LMD and compared the clinical data of LMD with TTN-mutated and mutation-free dilated cardiomyopathy to obtain the unique phenotype. After establishment of the LMNA c.357-2A>G primate model, primates were continuously observed for 48 months, and echocardiographic, electrophysiological, histologic, and transcriptional data were recorded. The LMD primate model was found to highly simulate the phenotype of clinical LMD. In addition, the LMD primate model shared a similar natural history with humans.

Keywords: CRISPR-mediated adenine base editing; dilated cardiomyopathy; lamin A/ C; primate model.