{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:31:16Z","timestamp":1790886676623,"version":"4.1.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>Cerebral cavernous malformation (CCM) is a brain vascular disease which can cause stroke, cerebral hemorrhage and neurological deficits in affected individuals. Loss-of-function mutations in three genes ( CCM1, CCM2 and CCM3) cause CCM disease. Multiple mouse models for CCM disease have been developed although each of them are associated with various limitations. Here, we employed the Dre-Cre dual recombinase system to specifically delete Ccm genes in brain endothelial cells. In this new series of CCM mouse models, robust CCM lesions now develop in the cerebrum. The survival curve and lesion burden analysis revealed that Ccm2 deletion causes modest CCM lesions with a median life expectance of \u223c10 months and Ccm3 gene deletion leads to the most severe CCM lesions with median life expectance of \u223c2 months. The extended lifespan of these mutant mice enables their utility in behavioral analyses of neurologic deficits in adult mice, and allow the development of methods to quantify lesion burden in mice over time and also permit longitudinal drug testing in live animals.<\/jats:p>","DOI":"10.1177\/0271678x221105995","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T07:27:27Z","timestamp":1654846047000},"page":"2230-2244","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Cerebral cavernous malformation development in chronic mouse models driven by dual recombinases induced gene deletion in brain endothelial cells"],"prefix":"10.1177","volume":"42","author":[{"given":"Xi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-9030","authenticated-orcid":false,"given":"Zifeng","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Vascular Epigenetics Laboratory, Victor Chang Cardiac Research Institute, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qichuan","family":"Zhuge","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Huang","sequence":"additional","affiliation":[{"name":"China National Clinical Research Centre for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"bibr1-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070972"},{"key":"bibr2-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318174"},{"key":"bibr3-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.02.004"},{"key":"bibr4-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03562-8"},{"key":"bibr5-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100440"},{"key":"bibr6-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.04.005"},{"key":"bibr7-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab117"},{"key":"bibr8-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1038\/nature17178"},{"key":"bibr9-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.004809"},{"key":"bibr10-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1038\/nature22075"},{"key":"bibr11-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110571"},{"key":"bibr12-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44393"},{"key":"bibr13-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20774-0"},{"key":"bibr14-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.027207"},{"key":"bibr15-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-020-09736-8"},{"key":"bibr16-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.029676"},{"key":"bibr17-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1038\/nature12207"},{"key":"bibr18-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau0731"},{"key":"bibr19-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312981"},{"key":"bibr20-0271678X221105995","unstructured":"National Research Council (US) committe for the update of the Guide for the Care and Use of Laboratory Animals.\n                      Guide for the Care and Use of Laboratory Animals\n                      , Eighth Edition, Washinton DC: The National Academies Press, 2011."},{"key":"bibr21-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20943823"},{"key":"bibr22-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.06.004"},{"key":"bibr23-0271678X221105995","doi-asserted-by":"crossref","first-page":"e0160833","DOI":"10.1371\/journal.pone.0160833","volume":"11","author":"Choi JP","year":"2016","journal-title":"PloS One"},{"key":"bibr24-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(72)90177-0"},{"key":"bibr25-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0590-4"},{"key":"bibr26-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1038\/nature13324"},{"key":"bibr27-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20947"},{"key":"bibr28-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.3634"},{"key":"bibr29-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq433"},{"key":"bibr30-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63409-8"},{"key":"bibr31-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn430"},{"key":"bibr32-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000157586.20479.fd"},{"key":"bibr33-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20915127"},{"key":"bibr34-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X21999553"},{"key":"bibr35-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10707-x"},{"key":"bibr36-0271678X221105995","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313970"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X221105995","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X221105995","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X221105995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:14:00Z","timestamp":1777493640000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X221105995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1177\/0271678X221105995"],"URL":"https:\/\/doi.org\/10.1177\/0271678x221105995","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,10]]}}}