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We used CRISPR-Cas9 mutagenesis to induce mosaic inactivation of zebrafish\n                    <jats:italic>ccm2<\/jats:italic>\n                    resulting in a novel lethal multi-cavernous lesion in the embryonic caudal venous plexus (CVP) caused by obstruction of blood flow by intraluminal pillars. These pillars mimic those that mediate intussusceptive angiogenesis; however, in contrast to the normal process, the pillars failed to fuse to split the pre-existing vessel in two. Abortive intussusceptive angiogenesis stemmed from mosaic inactivation of\n                    <jats:italic>ccm2<\/jats:italic>\n                    leading to patchy\n                    <jats:italic>klf2a<\/jats:italic>\n                    overexpression and resultant aberrant flow signaling. Surviving adult fish manifested histologically typical hemorrhagic CCM. Formation of mammalian CCM requires the flow-regulated transcription factor KLF2; fish CCM and the embryonic CVP lesion failed to form in\n                    <jats:italic>klf2a<\/jats:italic>\n                    null fish indicating a common pathogenesis with the mammalian lesion. These studies describe a zebrafish CCM model and establish a mechanism that can explain the formation of characteristic multi-cavernous lesions.\n                  <\/jats:p>","DOI":"10.7554\/elife.62155","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T08:00:27Z","timestamp":1621497627000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.62155","source":"Crossref","is-referenced-by-count":22,"title":["Abortive intussusceptive angiogenesis causes multi-cavernous vascular malformations"],"prefix":"10.7554","volume":"10","author":[{"given":"Wenqing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, United 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