IngentaConnect Transgenic mice aberrantly expressing pyruvate dehydrogenase comp...

Authors: Inamura, K.¹; Tsuji, H.¹; Nakamoto, Y.¹; Suzuki, M.²; Kaneko, S.

Source: Clinical & Experimental Immunology, Volume 145, Number 1, July 2006 , pp. 93-100(8)

Abstract:

Summary

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.

Keywords: biliary epithelial cell; primary biliary cirrhosis; pyruvate dehydrogenase complex E2 component; transgenic mouse

Document Type: Research article

DOI: 10.1111/j.1365-2249.2006.03090.x

Affiliations: 1: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa University, and 2: Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Japan

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Transgenic mice aberrantly expressing pyruvate dehydrogenase complex E2 component on biliary epithelial cells do not show primary biliary cirrhosis