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CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans

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, r...

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Autores principales: Yin, Xiaoyun, Hao, Jianxiu, Yao, Yuanqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580104/
https://www.ncbi.nlm.nih.gov/pubmed/34324266
http://dx.doi.org/10.1002/mgg3.1775
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author Yin, Xiaoyun
Hao, Jianxiu
Yao, Yuanqing
author_facet Yin, Xiaoyun
Hao, Jianxiu
Yao, Yuanqing
author_sort Yin, Xiaoyun
collection PubMed
description 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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spelling pubmed-85801042021-11-17 CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans Yin, Xiaoyun Hao, Jianxiu Yao, Yuanqing Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2021-07-29 /pmc/articles/PMC8580104/ /pubmed/34324266 http://dx.doi.org/10.1002/mgg3.1775 Text en © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Yin, Xiaoyun
Hao, Jianxiu
Yao, Yuanqing
CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans
title CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans
title_full CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans
title_fullStr CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans
title_full_unstemmed CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans
title_short CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans
title_sort crispr/cas9 in zebrafish: an attractive model for fbn1 genetic defects in humans
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580104/
https://www.ncbi.nlm.nih.gov/pubmed/34324266
http://dx.doi.org/10.1002/mgg3.1775
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AT yaoyuanqing crisprcas9inzebrafishanattractivemodelforfbn1geneticdefectsinhumans