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CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans
Author(s) -
Yin Xiaoyun,
Hao Jianxiu,
Yao Yuanqing
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1775
Subject(s) - zebrafish , crispr , biology , genetics , cas9 , gene , fibrillin , transgene , genome editing , frameshift mutation , marfan syndrome , mutation , medicine , surgery
Background Mutations in the fibrillin‐1 gene ( FBN1 ) are associated with various heritable connective tissue disorders (HCTD). The most studied HCTD is Marfan syndrome. Ninety percent of Marfan syndrome is caused by mutations in the FBN1 gene. The zebrafish share high genetic similarity to humans, representing an ideal model for genetic research of human diseases. This study aimed to generate and characterize fbn1 +/− mutant zebrafish using the CRISPR/Cas9 gene‐editing technology. Methods CRISPR/Cas9 was applied to generate an fbn1 frameshift mutation ( fbn1 +/− ) in zebrafish. F1 fbn1 +/− heterozygotes were crossed with transgenic fluorescent zebrafish to obtain F2 fbn1 +/− zebrafish. Morphological abnormalities were assessed in F2 fbn1 +/− zebrafish by comparing with the Tuebingen (TU) wild‐type controls at different development stages. Results We successfully generated a transgenic line of fbn1 +/− zebrafish. Compared with TU wild‐type zebrafish, F2 fbn1 +/− zebrafish exhibited noticeably decreased pigmentation, increased lengths, slender body shape, and abnormal cardiac blood flow from atrium to ventricle. Conclusion We generated the first fbn1 +/− zebrafish model using CRISPR/Cas9 gene‐editing approach to mimic FBN1 genetic defects in humans, providing an attractive model of Marfan syndrome and a method to determine the pathogenicity of gene mutation sites.

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