{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:25:13Z","timestamp":1790058313858,"version":"4.0.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2161,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,10]]},"abstract":"\n \n \n Anti-apoptotic members of the Bcl-2 family, including Bcl-2, Bcl-xL, Mcl-1, Bcl-w and Bfl-1, inhibit the mitochondrial pathway of apoptosis. Bcl-xL and Mcl-1 are constitutively expressed in the liver. Although previous research established Bcl-xL as a critical apoptosis antagonist in differentiated hepatocytes, the significance of Mcl-1 in the liver, especially in conjunction with Bcl-xL, has not been clear. To examine this question, we generated hepatocyte-specific Mcl-1\u2013deficient mice by crossing<\/jats:bold>\n mcl-1<\/jats:bold>\n flox\n \n \/\n \n flox<\/jats:sup>\n mice and<\/jats:bold>\n AlbCre<\/jats:bold>\n mice and further crossed them with<\/jats:bold>\n bcl-x<\/jats:bold>\n flox\n \n \/\n \n flox<\/jats:sup>\n mice, giving Mcl-1\/Bcl-xL\u2013deficient mice. The<\/jats:bold>\n mcl-1<\/jats:bold>\n flox\n \n \/\n \n flox<\/jats:sup>\n AlbCre<\/jats:bold>\n mice showed spontaneous apoptosis of hepatocytes after birth, as evidenced by elevated levels of serum alanine aminotransferase (ALT) and caspase-3\/7 activity and an increased number of terminal deoxynucleotidyl transferase-mediated 2\u2032-deoxyuridine 5\u2032-triphosphate nick-end labeling (TUNEL)-positive cells in the liver; these phenotypes were very close to those previously found in hepatocyte-specific Bcl-xL\u2013deficient mice. Although<\/jats:bold>\n mcl-1<\/jats:bold>\n flox\n \n \/+<\/jats:sup>\n AlbCre<\/jats:bold>\n mice did not display apoptosis, their susceptibility to Fas-mediated liver injury significantly increased. Further crossing of Mcl-1 mice with Bcl-xL mice showed that<\/jats:bold>\n bcl-x<\/jats:bold>\n flox\n \n \/+<\/jats:sup>\n mcl-1<\/jats:bold>\n flox\n \n \/+<\/jats:sup>\n AlbCre<\/jats:bold>\n mice also showed spontaneous hepatocyte apoptosis similar to Bcl-xL\u2013deficient or Mcl-1\u2013deficient mice. In contrast,<\/jats:bold>\n bcl-x<\/jats:bold>\n flox\n \n \/\n \n flox<\/jats:sup>\n mcl-1<\/jats:bold>\n flox\n \n \/+<\/jats:sup>\n AlbCre<\/jats:bold>\n ,<\/jats:bold>\n bcl-x<\/jats:bold>\n flox\n \n \/+<\/jats:sup>\n mcl-1<\/jats:bold>\n flox\n \n \/\n \n flox<\/jats:sup>\n AlbCre,<\/jats:bold>\n and<\/jats:bold>\n bcl-x<\/jats:bold>\n flox\n \n \/\n \n flox<\/jats:sup>\n mcl-1<\/jats:bold>\n flox\n \n \/\n \n flox<\/jats:sup>\n AlbCre<\/jats:bold>\n mice displayed a decreased number of hepatocytes and a reduced volume of the liver on day 18.5 of embryogenesis and rapidly died within 1 day after birth, developing hepatic failure evidenced by increased levels of blood ammonia and bilirubin.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Mcl-1 is critical for blocking apoptosis in adult liver and, in the absence of Bcl-xL, is essential for normal liver development. Mcl-1 and Bcl-xL are two major anti-apoptotic Bcl-2 family proteins expressed in the liver and cooperatively control hepatic integrity during liver development and in adult liver homeostasis in a gene dose-dependent manner. (Hepatology 2009.)<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.23126","type":"journal-article","created":{"date-parts":[[2009,6,15]],"date-time":"2009-06-15T14:32:48Z","timestamp":1245076368000},"page":"1217-1226","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":125,"title":["Mcl-1 and Bcl-xL Cooperatively Maintain Integrity of Hepatocytes in Developing and Adult Murine 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