{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:22:48Z","timestamp":1790709768576,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations in the fibrillin\u20101 gene (<jats:italic>FBN1<\/jats:italic>) 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 <jats:italic>FBN1<\/jats:italic> 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 <jats:italic>fbn1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mutant zebrafish using the CRISPR\/Cas9 gene\u2010editing technology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CRISPR\/Cas9 was applied to generate an <jats:italic>fbn1<\/jats:italic> frameshift mutation (<jats:italic>fbn1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>) in zebrafish. F1 <jats:italic>fbn1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> heterozygotes were crossed with transgenic fluorescent zebrafish to obtain F2 <jats:italic>fbn1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> zebrafish. Morphological abnormalities were assessed in F2 <jats:italic>fbn1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> zebrafish by comparing with the Tuebingen (TU) wild\u2010type controls at different development stages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We successfully generated a transgenic line of <jats:italic>fbn1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> zebrafish. Compared with TU wild\u2010type zebrafish, F2 <jats:italic>fbn1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> zebrafish exhibited noticeably decreased pigmentation, increased lengths, slender body shape, and abnormal cardiac blood flow from atrium to ventricle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We generated the first <jats:italic>fbn1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> zebrafish model using CRISPR\/Cas9 gene\u2010editing approach to mimic <jats:italic>FBN1<\/jats:italic> genetic defects in humans, providing an attractive model of Marfan syndrome and a method to determine the pathogenicity of gene mutation sites.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1775","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T13:39:16Z","timestamp":1627565956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["CRISPR\/Cas9 in zebrafish: An 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