{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:52:35Z","timestamp":1790275955320,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4292,"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":[[2003,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Intrahepatic cholestasis is often associated with impairment of biliary bile acid secretion, a process mediated by the sister of P\u2013glycoprotein (Spgp or Abcb11) also known as the bile salt export pump (Bsep). In humans, mutations in the Spgp gene are associated with a fatal childhood disease, type 2 progressive familial intrahepatic cholestasis (PFIC2). However in mice, the \u201cknockout\u201d of Spgp only results in mild cholestasis. In this study, we fed <jats:italic toggle=\"yes\">spgp<\/jats:italic>\n                                 <jats:sup>-\/-<\/jats:sup> knockout mice with a cholic acid (CA)\u2013supplemented diet to determine whether a more pronounced PFIC2\u2013like phenotype could be induced. Such mice developed severe cholestasis characterized by jaundice, weight loss, elevated plasma bile acid, elevated transaminase, cholangiopathy (proliferation of bile ductules and cholangitis), liver necrosis, high mortality, and wide\u2013ranging changes in the mRNA expression of major liver genes (16\/36 examined). A surprising observation was that the bile acid output and bile flow in CA\u2013fed mutant mice was significantly higher than anticipated. This suggests that the <jats:italic toggle=\"yes\">spgp<\/jats:italic>\n                                 <jats:sup>-\/-<\/jats:sup> mice are able to utilize an alternative bile salt transport system. However, unlike Spgp, this system is insufficient to protect the knockout mice from cholestasis despite its high capacity. In conclusion, the <jats:italic toggle=\"yes\">spgp<\/jats:italic>\n                                 <jats:sup>-\/-<\/jats:sup> mice provide a unique model to investigate molecular pathways associated with cholestasis and related diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1016\/j.hep.2003.09.037","type":"journal-article","created":{"date-parts":[[2003,11,25]],"date-time":"2003-11-25T20:29:01Z","timestamp":1069792141000},"page":"1489-1499","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":66,"title":["Severe Cholestasis Induced by Cholic Acid Feeding in Knockout Mice of Sister of P\u2013Glycoprotein"],"prefix":"10.1097","volume":"38","author":[{"given":"Renxue","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Forrest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M.","family":"Yousef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Mignault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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