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We previously reported a recessive missense mutation, meltdown (mlt), which converts a highly conserved tryptophan to arginine (W512R) in the rigid relay loop of zebrafish Myh11. The mlt mutation disrupts myosin regulation and non-autonomously induces invasive expansion of the intestinal epithelium. Here, we report two newly identified missense mutations in the switch-1 (S237Y) and coil-coiled (L1287M) domains of Myh11 that fail to complement mlt. Cell invasion was not detected in either homozygous mutant but could be induced by oxidative stress and activation of oncogenic signaling pathways. The smooth muscle defect imparted by the mlt and S237Y mutations also delayed intestinal transit, and altered vascular function, as measured by blood flow in the dorsal aorta. The cell-invasion phenotype induced by the three myh11 mutants correlated with the degree of myosin deregulation. These findings suggest that the vertebrate intestinal epithelium is tuned to the physical state of the surrounding stroma, which, in turn, governs its response to physiologic and pathologic stimuli. Genetic variants that alter the regulation of smooth muscle myosin might be risk factors for diseases affecting the intestine, vasculature, and other tissues that contain smooth muscle or contractile cells that express smooth muscle proteins, particularly in the setting of redox stress.<\/jats:p>","DOI":"10.1242\/dmm.023309","type":"journal-article","created":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T04:18:00Z","timestamp":1455855480000},"page":"529-540","source":"Crossref","is-referenced-by-count":13,"title":["Graded effects of unregulated smooth muscle myosin on intestinal architecture, intestinal motility and vascular function in zebrafish"],"prefix":"10.1242","volume":"9","author":[{"given":"Joshua","family":"Abrams","sequence":"first","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania 1 Department of Medicine , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zev","family":"Einhorn","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania 1 Department of Medicine , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Seiler","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania 1 Department of Medicine , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan B.","family":"Zong","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania 2 Department of Physiology , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Lee","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania 2 Department of Physiology , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pack","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania 1 Department of Medicine , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061302521385100_DMM023309C1","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/j.1365-2982.2011.01844.x","article-title":"Smooth muscle caldesmon modulates peristalsis in the wild type and non-innervated zebrafish intestine","volume":"24","author":"Abrams","year":"2012","journal-title":"Neurogastroenterol. 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