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Attempt of producing an experimental animal model of biliary atresia using bcl-2 knock-out mice : the analysis of bcl-2 as the apoptosis inhibitor in biliary atresia

Research Project

Project/Area Number 11557129
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Pediatric surgery
Research InstitutionTohoku University

Principal Investigator

OHI Ryoji  Tohoku University, school of Medicine, Professor, 大学院・医学系研究科, 教授 (50004734)

Co-Investigator(Kenkyū-buntansha) NIO Masaki  Tohoku University, school of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70228138)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥9,600,000 (Direct Cost: ¥9,600,000)
Keywordsbiliary atresia / apoptosis / bcl-2 / knock-out mouse / inv / cytokine
Research Abstract

As the expression of the bcl-2 gene is analyzed by using the liver biopsy sample at the time of the operation for biliary atresia it has become clear that lower expression of the bcl-2 gene in the liver specimen from patients with biliary atresia than those from controls. Thereupon, we tried to study the liver disease of biliary atresia using the bcl-2 knock-out mouse.
Bcl-2 knock-out mice did not survive long enough to be appropriately evaluated. We paid attention to the inv variant mouse that happens to be complicated by cholestasis as well as situs inversus. Furthermore we are studying inv status in biliary atresia patients associated with situs inversus using their blood samples. These studies should elucidate the role of apoptosis inhibitory genes and inv genes in the pathogenesis of biliary atresia.
Abnormally progressed apoptosis resulting in diffuse cholangitis would lead to inflammatory catastrophe all over the liver. We already disclosed the significant roles of the various kinds of fibrinogenic cytokines, mast cell, c-kit, and CD14 in the inflammatory process in biliary atresia. While hepatocytes and intrahepatic bile ducts can regenerate enough during and immediately after the embryonal period even when they are severely damaged, extrahepatic biliary atresia is irreversible. We hypothesized that biliary atresia is ultimately established in these process above

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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