title: Liver fibrosis during the development of biliary atresia: Proof of principle in the murine model.
abstract: BACKGROUND
  The murine model of biliary atresia (BA) is used for examining the pathogenesis of BA. The aim of the study was description of the morphological features and illustrating the detailed development of fibrosis using the Biliary Atresia Research Consortium (BARC) system.
  
  
  METHODS
  Neonatal mice were injected intraperitoneally with rhesus rotavirus (RRV) strain (N=17). Healthy mice were the control group (N=29). All mice were sacrificed at 7 or 14days after birth. Two pathologists examined the morphological features using the BARC system; CK19, αSMA and collagen type I were assessed by immunohistochemistry.
  
  
  RESULTS
  In RRV mice, portal fibrous expansion with focal bile duct proliferation and strong portal cellular infiltrate was found in contrast to healthy mice. In RRV mice, CK19 bile duct staining was significantly less or absent (p<0.01), with stronger portal staining of collagen type I (p=0.02). Expansion of staining for αSMA was more in RRV mice (p<0.01), but αSMA portal staining was stronger in healthy mice (p=0.02).
  
  
  CONCLUSIONS
  The morphological features observed in the murine model of BA correspond with the BA characteristics according to the BARC criteria. Fibrosis is an important feature of the model. Therefore, this murine model is useful for investigating the pathogenesis of BA.
authors.affiliation: Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands; Department of Pediatric Surgery, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Claudia M G
authors.initials: CM
authors.lastname: Keyzer-Dekker
authors.affiliation: Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
authors.forename: Robert Cornelis
authors.initials: RC
authors.lastname: Lind
authors.affiliation: Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: J F
authors.initials: JF
authors.lastname: Kuebler
authors.affiliation: Department of Pathology, University Medical Centre Utrecht, The Netherlands.
authors.forename: G J A
authors.initials: GJ
authors.lastname: Offerhaus
authors.affiliation: Department of Pathology, University Medical Centre Utrecht, The Netherlands.
authors.forename: F J W
authors.initials: FJ
authors.lastname: Ten Kate
authors.affiliation: Department of Pathology, University Medical Centre Utrecht, The Netherlands.
authors.forename: F H M
authors.initials: FH
authors.lastname: Morsink
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Verkade
authors.affiliation: Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands. Electronic address: j.b.f.hulscher@umcg.nl.
authors.forename: J B F
authors.initials: JB
authors.lastname: Hulscher
mesh_terms: D000818:Animals; D001656:Biliary Atresia / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D018450:Disease Progression; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012400:Rotavirus Infections / Q000150:complications; D012720:Severity of Illness Index
keywords: Biliary atresia; Fibrosis; Immunohistochemistry; Rhesus rotavirus murine model