Pediatric Surgery International

, Volume 22, Issue 1, pp 84–89 | Cite as

Gene expression profile of the infective murine model for biliary atresia

  • Johannes Leonhardt
  • Martin Stanulla
  • Reinhard von Wasielewski
  • Julia Skokowa
  • Joachim Kübler
  • Benno M. Ure
  • Claus Petersen
Original Article

Abstract

One hypothesis of the pathogenesis of biliary atresia (BA) is a virus-induced and immune-mediated injury to bile duct cells as mimicked in the rotavirus-induced murine model. This theory is supported by studies showing a predominant T helper cell response type 1-like phenotype of inflammation with increased interferon gamma-induced chemokines in the liver of humans and mice suffering from BA. Recent gene expression profiling studies using microarray analysis showed the induction of a proinflammatory state in human liver specimens with high analogies in extrahepatic biliary tissue of BA mice. The aim of the present study was a microarray analysis of gene expression in the liver of Balb/c mice, comparing infected mice that show the phenotype of BA versus infected mice without symptoms, thus trying to elucidate genes that are not related to the viral origin of this model, but to the specific pathogenesis of the clinical picture of BA. Fifteen μg of RNA, each of three BA-positive and three BA-negative mice, were pooled and comparatively hybridized to spotted cDNA microarrays containing 250 key genes with high relevance to immunological settings. We identified the 40 genes most differentially expressed in mice with and without BA. The majority of genes with higher expression in BA-positive mice encoded proinflammatory cytokines involved in the Th1 pathway, such as CCL2, CCL5, CCR5, CXCL10, CCL2, IL1F5 and in apoptosis, such as DDR3 and granzyme A and B. In this initial study of the molecular characterization of our RRV-induced BA mouse model system, we also found potential novel candidates important to BA etiology, such as growth hormone receptor and insulin-like growth factor. Of particular interest, very low expression of TIMD2 was observed in BA-positive mice. TIMD2 plays a critical role in the regulation of a Th2-type response through the inhibition of IFN gamma.

Keywords

Bile Duct Biliary Atresia Extrahepatic Bile Duct Growth Hormone Receptor Specific Pathogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors would like to thank Ms Birgit Teichmann for technical assistance and Ms Clare Boerner for revising the text. This work was supported by a grant (HiLFI) from the Hannover Medical School, Germany.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Johannes Leonhardt
    • 1
  • Martin Stanulla
    • 2
  • Reinhard von Wasielewski
    • 3
  • Julia Skokowa
    • 2
  • Joachim Kübler
    • 1
  • Benno M. Ure
    • 1
  • Claus Petersen
    • 1
  1. 1.Department of Pediatric SurgeryHannover Medical SchoolHannoverGermany
  2. 2.Department of Pediatric Hematology and Oncology Hannover Medical SchoolHannoverGermany
  3. 3.Department of PathologyHannover Medical SchoolHannoverGermany

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