title: Induction of experimental obstructive cholestasis in mice.
abstract: The induction of experimental obstructive cholestasis is a reliable model for cholestatic liver diseases in rodents. Bile duct ligation (BDL) in mice provokes typical time-dependent morphological and structural changes in the liver, ranging from liver cell injury and elevated serum enzyme levels after several days, to a severe inflammatory response in the liver after 5-7 days, up to an advanced hepatic fibrosis as soon as three to four weeks after surgical ligation of the common biliary duct. Upon BDL induction, hepatic stellate cells become activated and transdifferentiate into myofibroblasts that produce extracellular matrix proteins such as collagen. In principle, the periportal fibrosis induced by BDL in rat livers is reversible. After the relief of a biliary obstruction, the liver has the capacity to revert to a nearly normal histological architecture and a fully normal biochemical function. When BDL surgery is performed by an experienced scientist, this model has very high reproducibility among all fibrotic models. All these factors corroborate the outstanding value of this model for basic and translational research in biomedicine and hepatology. Nevertheless, this model can result in significant variations when surgery is carried out by untrained personnel or when unconscious modifications are implemented that affect the quality of the intervention. A detailed protocol is provided here for the provision of reliable and reproducible BDL in mice.
authors.affiliation: Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen, Germany.
authors.forename: C G
authors.initials: CG
authors.lastname: Tag
authors.affiliation: Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Weiskirchen
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hittatiya
authors.affiliation: Department of Medicine III, RWTH University Hospital Aachen, Aachen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Tacke
authors.affiliation: Institute of Laboratory Animal Science and Experimental Surgery, RWTH University Aachen, Aachen, Germany for the Transregional Collaborative Research Center 'Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease' (SFB/TRR57).
authors.forename: R H
authors.initials: RH
authors.lastname: Tolba
authors.affiliation: Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen, Germany rweiskirchen@ukaachen.de.
authors.forename: R
authors.initials: R
authors.lastname: Weiskirchen
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000601:surgery*; D002779:Cholestasis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D017408:Guidelines as Topic; D006801:Humans; D007756:Laboratory Animal Science / Q000592:standards; D008026:Ligation; D051379:Mice
keywords: biliary obstruction; cell infiltration; cirrhosis; fibrosis; jaundice