{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:15:04Z","timestamp":1790892904218,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T00:00:00Z","timestamp":1541635200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>We report the genetic analysis of a \u201chumanized\u201d hyperlipidemic mouse model for progressive nonalcoholic steatohepatitis (NASH) and fibrosis. Mice carrying transgenes for human apolipoprotein E*3\u2010Leiden and cholesteryl ester transfer protein and fed a \u201cWestern\u201d diet were studied on the genetic backgrounds of over 100 inbred mouse strains. The mice developed hepatic inflammation and fibrosis that was highly dependent on genetic background, with vast differences in the degree of fibrosis. Histological analysis showed features characteristic of human NASH, including macrovesicular steatosis, hepatocellular ballooning, inflammatory foci, and pericellular collagen deposition. Time course experiments indicated that while hepatic triglyceride levels increased steadily on the diet, hepatic fibrosis occurred at about 12 weeks. We found that the genetic variation predisposing to NASH and fibrosis differs markedly from that predisposing to simple steatosis, consistent with a multistep model in which distinct genetic factors are involved. Moreover, genome\u2010wide association identified distinct genetic loci contributing to steatosis and NASH. Finally, we used hepatic expression data from the mouse panel and from 68 bariatric surgery patients with normal liver, steatosis, or NASH to identify enriched biological pathways. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> The pathways showed substantial overlap between our mouse model and the human disease.<\/jats:p>","DOI":"10.1002\/hep.30113","type":"journal-article","created":{"date-parts":[[2018,6,16]],"date-time":"2018-06-16T08:25:50Z","timestamp":1529137550000},"page":"2182-2196","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":66,"title":["The Genetic Architecture of Diet\u2010Induced Hepatic Fibrosis in Mice"],"prefix":"10.1097","volume":"68","author":[{"given":"Simon T.","family":"Hui","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiology,David Geffen School of Medicine,Los 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