title: Transgenic mice aberrantly expressing pyruvate dehydrogenase complex E2 component on biliary epithelial cells do not show primary biliary cirrhosis.
abstract: Primary biliary cirrhosis (PBC) is an autoimmune disorder that specifically destroys biliary epithelial cells (BECs). In patients with PBC, the immunodominant pyruvate dehydrogenase complex E2 component (PDC-E2), identified as an antigen for disease-specific anti-mitochondrial antibody, is expressed aberrantly in the BEC cytoplasm. The present study focused on the pathophysiological role of aberrant PDC-E2 in the development of PBC. The BEC-specific cytokeratin-19 promoter and PDC-E2 gene were cloned from a mouse cDNA library. The constructed transgene was microinjected into fertilized eggs of mice, and the offspring were identified by Southern blotting and reverse transcriptase-polymerase chain reaction. The protein expression was confirmed by immunoprecipitation, immunoblotting and immunohistochemical staining. Five founder lines were identified as carrying the PDC-E2 gene, and one of these lines expressed PDC-E2 mRNA. The protein expression of exogenous PDC-E2 was detected in the liver. The transgenic mouse line showed diffuse expression of PDC-E2 in the BEC cytoplasm. Biochemical, serological and histological features of PBC were not detected. We established transgenic mice that constitutively express PDC-E2. The results indicated that aberrant PDC-E2 expression in the cytoplasm of BECs is not sufficient for the initiation of autoimmunity. Additional factors may be required to establish a model of PBC.
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa University, Kanazawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inamura
authors.forename: H
authors.initials: H
authors.lastname: Tsuji
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001659:Biliary Tract / Q000201:enzymology*; D015153:Blotting, Western / Q000379:methods; D003593:Cytoplasm / Q000201:enzymology; D051047:Dihydrolipoyllysine-Residue Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology*; D005818:Genetic Engineering; D047468:Immunoprecipitation; D007633:Keratins / Q000235:genetics; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000201:enzymology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007633:Keratins; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase