| First Author | Inamura K | Year | 2006 |
| Journal | Clin Exp Immunol | Volume | 145 |
| Issue | 1 | Pages | 93-100 |
| PubMed ID | 16792678 | Mgi Jnum | J:110166 |
| Mgi Id | MGI:3639536 | Doi | 10.1111/j.1365-2249.2006.03090.x |
| Citation | Inamura K, et al. (2006) Transgenic mice aberrantly expressing pyruvate dehydrogenase complex E2 component on biliary epithelial cells do not show primary biliary cirrhosis. Clin Exp Immunol 145(1):93-100 |
| abstractText | 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. |
