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Despite clinical variability, the majority of patients harbour a <jats:italic><jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content><\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>816<jats:styled-content style=\"fixed-case\">V<\/jats:styled-content> mutation, but efforts to inhibit mutant <jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content> with tyrosine kinase inhibitors have been unsatisfactory, indicating a need for new preclinical approaches to identify alternative targets and novel therapies in this disease. Murine models to date have been limited and do not fully recapitulate the most aggressive forms of <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>. We describe the generation of a transgenic zebrafish model expressing the human <jats:italic><jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content><\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>816<jats:styled-content style=\"fixed-case\">V<\/jats:styled-content> mutation. Adult fish demonstrate a myeloproliferative disease phenotype, including features of aggressive <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> in haematopoeitic tissues and high expression levels of endopeptidases, consistent with <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> patients. Transgenic embryos demonstrate a cell\u2010cycle phenotype with corresponding expression changes in genes associated with <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> maintenance and repair, such as reduced <jats:italic>dnmt1<\/jats:italic>. In addition, <jats:italic>epcam<\/jats:italic> was consistently downregulated in both transgenic adults and embryos. Decreased embryonic <jats:italic>epcam<\/jats:italic> expression was associated with reduced neuromast numbers, providing a robust <jats:italic>in vivo<\/jats:italic> phenotypic readout for chemical screening in <jats:italic><jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content><\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>816<jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>\u2010induced disease. This study represents the first zebrafish model of a mast cell disease with an aggressive adult phenotype and embryonic markers that could be exploited to screen for novel agents in <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.12999","type":"journal-article","created":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T14:29:05Z","timestamp":1404311345000},"page":"48-61","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A transgenic zebrafish model expressing <i><scp>KIT<\/scp><\/i>\u2010<scp>D<\/scp>816<scp>V<\/scp> recapitulates features of aggressive systemic mastocytosis"],"prefix":"10.1111","volume":"167","author":[{"given":"Tugce B.","family":"Balci","sequence":"first","affiliation":[{"name":"Department of Pediatrics IWK Health Centre Halifax NS Canada"},{"name":"Department of Medical Genetics University of Ottawa Ottawa ON 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