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

Abstract 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 h...

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Autores principales:	Xiaoyun Yin, Jianxiu Hao, Yuanqing Yao
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	animal model CRISPR/Cas9 fibrillin‐1 Marfan syndrome zebrafish Genetics QH426-470
Acceso en línea:	https://doaj.org/article/9a6324a801544611ac8a976bc134c313
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spelling	oai:doaj.org-article:9a6324a801544611ac8a976bc134c3132021-11-10T16:39:23ZCRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans2324-926910.1002/mgg3.1775https://doaj.org/article/9a6324a801544611ac8a976bc134c3132021-10-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1775https://doaj.org/toc/2324-9269Abstract 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.Xiaoyun YinJianxiu HaoYuanqing YaoWileyarticleanimal modelCRISPR/Cas9fibrillin‐1Marfan syndromezebrafishGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	animal model CRISPR/Cas9 fibrillin‐1 Marfan syndrome zebrafish Genetics QH426-470
spellingShingle	animal model CRISPR/Cas9 fibrillin‐1 Marfan syndrome zebrafish Genetics QH426-470 Xiaoyun Yin Jianxiu Hao Yuanqing Yao CRISPR/Cas9 in zebrafish: An attractive model for FBN1 genetic defects in humans
description	Abstract 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.
format	article
author	Xiaoyun Yin Jianxiu Hao Yuanqing Yao
author_facet	Xiaoyun Yin Jianxiu Hao Yuanqing Yao
author_sort	Xiaoyun Yin
title	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_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_sort	crispr/cas9 in zebrafish: an attractive model for fbn1 genetic defects in humans
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/9a6324a801544611ac8a976bc134c313
work_keys_str_mv	AT xiaoyunyin crisprcas9inzebrafishanattractivemodelforfbn1geneticdefectsinhumans AT jianxiuhao crisprcas9inzebrafishanattractivemodelforfbn1geneticdefectsinhumans AT yuanqingyao crisprcas9inzebrafishanattractivemodelforfbn1geneticdefectsinhumans
_version_	1718439894238363648

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

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