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To determine whether\n                    <jats:italic>ORMDL3<\/jats:italic>\n                    selective expression in airway smooth muscle (ASM) influences ASM function, we used Cre-\n                    <jats:italic>loxP<\/jats:italic>\n                    techniques to generate transgenic mice (\n                    <jats:italic>hORMDL3<\/jats:italic>\n                    <jats:sup>Myh11eGFP-cre<\/jats:sup>\n                    ), which express human ORMDL3 selectively in smooth muscle cells. In vitro studies of ASM cells isolated from the bronchi of\n                    <jats:italic>hORMDL3<\/jats:italic>\n                    <jats:sup>Myh11eGFP-cre<\/jats:sup>\n                    mice demonstrated that they developed hypertrophy (quantitated by FACS and image analysis), developed hyperplasia (assessed by BrdU incorporation), and expressed increased levels of tropomysin proteins TPM1 and TPM4. siRNA knockdown of TPM1 or TPM4 demonstrated their importance to ORMDL3-mediated ASM proliferation but not hypertrophy. In addition, ASM derived from\n                    <jats:italic>hORMDL3<\/jats:italic>\n                    <jats:sup>Myh11eGFP-cre<\/jats:sup>\n                    mice had increased contractility to histamine in vitro, which was associated with increased levels of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ; increased cell surface membrane Orai1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels, which mediate influx of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    into the cytoplasm; and increased expression of ASM contractile genes sarco\/endoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ATPase 2b and smooth muscle 22. In vivo studies of\n                    <jats:italic>hORMDL3<\/jats:italic>\n                    <jats:sup>Myh11eGFP-cre<\/jats:sup>\n                    mice demonstrated that they had a spontaneous increase in ASM and airway hyperreactivity (AHR).\n                    <jats:italic>ORMDL3<\/jats:italic>\n                    expression in ASM thus induces changes in ASM (hypertrophy, hyperplasia, increased contractility), which may explain the contribution of\n                    <jats:italic>ORMDL3<\/jats:italic>\n                    to the development of AHR in childhood onset asthma, which is highly linked to\n                    <jats:italic>ORMDL3<\/jats:italic>\n                    on chromosome 17q12-21.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.136911","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T12:00:42Z","timestamp":1614859242000},"source":"Crossref","is-referenced-by-count":17,"title":["ORMDL3 expression in ASM regulates hypertrophy, hyperplasia via TPM1 and TPM4, and contractility"],"prefix":"10.1172","volume":"6","author":[{"given":"Alexa K.","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudipta","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, California, 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