Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

Lin Zhu; Xiaoyan Yang; Juyi Li; Xiong Jia; Xiangli Bai; Ying Zhao; Wenzhuo Cheng; Meng Shu; Yan Zhu; Si Jin

doi:10.1016/j.jgg.2021.01.008

Volume 48 Issue 2

Feb. 2021

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Article Navigation > Journal of Genetics and Genomics > 2021 > 48(2): 134-146

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Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

doi: 10.1016/j.jgg.2021.01.008

Lin Zhu^{a, b},
Xiaoyan Yang^c,
Juyi Li^d,
Xiong Jia^a,
Xiangli Bai^{a, e},
Ying Zhao^a,
Wenzhuo Cheng^a,
Meng Shu^a,
Yan Zhu^a,
Si Jin^{a, c}

a
Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
b
Department of Pediatrics, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, Wuhan 430030, China
c
Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
d
Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
e
Department of Laboratory Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

More Information

Corresponding author: E-mail address: Jinsi@hust.edu.cn (Si Jin)
Received Date: 2020-10-27
Accepted Date: 2021-01-28
Rev Recd Date: 2021-01-25

Available Online: 2021-03-30

Publish Date: 2021-02-20

Abstract

Abstract

Gene therapy has become the most effective treatment for monogenic diseases. Congenital LEPTIN deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the Leptin gene. Ob/ob mouse is a monogenic obesity model, which carries a homozygous point mutation of C to T in Exon 2 of the Leptin gene. Here, we attempted to edit the mutated Leptin gene in ob/ob mice preadipocytes and inguinal adipose tissues using CRISPR/Cas9 to correct the C to T mutation and restore the production of LEPTIN protein by adipocytes. The edited preadipocytes exhibit a correction of 5.5% ofLeptin alleles and produce normal LEPTIN protein when differentiated into mature adipocytes. The ob/ob mice display correction of 1.67% of Leptin alleles, which is sufficient to restore the production and physiological functions of LEPTIN protein, such as suppressing appetite and alleviating insulin resistance. Our study suggests CRISPR/Cas9-mediated in situ genome editing as a feasible therapeutic strategy for human monogenic diseases, and paves the way for further research on efficient delivery system in potential future clinical application.
- CRISPR/Cas9,
- Gene editing,
- Leptin,
- Monogenetic disease,
- Obesity

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References(34)

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