Skip to main content
SpringerLink
Log in
Book cover

Experimental Cholestasis Research pp 259–271Cite as

A Rotavirus-Induced Mouse Model to Study Biliary Atresia and Neonatal Cholestasis

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1981))

Abstract

Biliary atresia is a devastating neonatal cholangiopathy that affects both extra- and intrahepatic bile ducts progressing to fibrosis and end-stage liver disease by 2 years of age. Despite re-establishment of biliary drainage following a Kasai portoenterostomy (surgical procedure), many infants develop fibrosis requiring liver transplant. In the murine model of biliary atresia, rhesus rotavirus infection of newborn pups results in a cholangiopathy paralleling human biliary atresia and is used to study mechanistic aspects of the disease. The infected mice displayed histopathological signs similar to human biliary atresia, with bile duct obstruction, bile duct proliferation, and liver inflammation with fibrosis.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Chardot C, Buet C, Serinet MO et al (2013) Improving outcomes of biliary atresia: French national series 1986–2009. J Hepatol 58:1209–1217

    Article  Google Scholar 

  2. Diem HV, Evrard V, Vinh HT et al (2003) Pediatric liver transplantation for biliary atresia: results of primary grafts in 328 recipients. Transplantation 75:1692–1697

    Article  Google Scholar 

  3. Serinet MO, Wildhaber BE, Broue P et al (2009) Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics 123:1280–1286

    Article  Google Scholar 

  4. McDiarmid SV (2000) Liver transplantation. the pediatric challenge. Clin Liver Dis 4:879–927

    Article  CAS  Google Scholar 

  5. Ohi R, Hanamatsu M, Mochizuki I et al (1985) Progress in the treatment of biliary atresia. World J Surg 9:285–293

    Article  CAS  Google Scholar 

  6. Kelly DA (2003) Strategies for optimizing immunosuppression in adolescent transplant recipients: a focus on liver transplantation. Paediatr Drugs 3:177–183

    Article  Google Scholar 

  7. Marchetti P (2004) New-onset diabetes after transplantation. J Heart Lung Transplant 23:S194–S201

    Article  Google Scholar 

  8. Seipelt IM, Crawford SE, Rodgers S et al (2004) Hypercholesterolemia is common after pediatric heart transplantation: initial experience with pravastatin. J Heart Lung Transplant 23:317–322

    Article  Google Scholar 

  9. Dharnidharka VR, Tejani AH, Ho PL et al (2002) Post-transplant lymphoproliferative disorder in the United States: young Caucasian males are at highest risk. Am J Transplant 2:993–998

    Article  Google Scholar 

  10. Landing BH (1974) Considerations of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst-the concept of infantile obstructive cholangiopathy. Prog Pediatr Surg 6:113–139

    CAS  Google Scholar 

  11. Qiao H, Zhaori G, Jiang Z et al (1999) Detection of group C rotavirus antigen in bile duct and liver tissues of an infant with extrahepatic biliary atresia. Chin Med J 112:93–95

    CAS  Google Scholar 

  12. Riepenhoff-Talty M, Gouvea V, Evans MJ et al (1996) Detection of group C rotavirus in infants with extrahepatic biliary atresia. J Infect Dis 174:8–15

    Article  CAS  Google Scholar 

  13. Glaser JH, Balistreri WF, Morecki R (1984) Role of reovirus type 3 in persistent infantile cholestasis. J Pediatr 105:912–915

    Article  CAS  Google Scholar 

  14. Morecki R, Glaser JH, Cho S et al (1982) Biliary atresia and reovirus type 3 infection. N Engl J Med 307:481–484

    Article  CAS  Google Scholar 

  15. Morecki R, Glaser JH, Cho S (1984) Biliary atresia and reovirus type 3 infection. N Engl J Med 310:1610

    CAS  Google Scholar 

  16. Domiati-Saad R, Dawson DB, Margraf LR et al (2000) Cytomegalovirus and human herpesvirus 6, but not human papillomavirus, are present in neonatal giant cell hepatitis and extrahepatic biliary atresia. Pediatr Dev Pathol 3:367–373

    Article  CAS  Google Scholar 

  17. Fischler B, Ehrnst A, Forsgren M et al (1998) The viral association of neonatal cholestasis in Sweden: a possible link between cytomegalovirus infection and extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 27:57–64

    Article  CAS  Google Scholar 

  18. Drut R, Drut RM, Gomez MA et al (1998) Presence of human papillomavirus in extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 27:530–535

    Article  CAS  Google Scholar 

  19. Mack CL (2007) The pathogenesis of biliary atresia: evidence for a virus-induced autoimmune disease. Semin Liver Dis 27:233–242

    Article  CAS  Google Scholar 

  20. Sokol RJ, Mack C (2001) Etiopathogenesis of biliary atresia. Semin Liver Dis 21:517–524

    Article  CAS  Google Scholar 

  21. Bezerra JA, Tiao G, Ryckman FC et al (2002) Genetic induction of proinflammatory immunity in children with biliary atresia. Lancet 360:1653–1659

    Article  Google Scholar 

  22. Mohanty SK, Ivantes CA, Mourya R et al (2010) Macrophages are targeted by rotavirus in experimental biliary atresia and induce neutrophil chemotaxis by Mip2/Cxcl2. Pediatr Res 67:345–351

    Article  CAS  Google Scholar 

  23. Shivakumar P, Sabla GE, Whitington P et al (2009) Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia. J Clin Invest 119:2281–2290

    Article  CAS  Google Scholar 

  24. Walther A, Mohanty SK, Donnelly B et al (2015) Rhesus rotavirus VP4 sequence-specific activation of mononuclear cells is associated with cholangiopathy in murine biliary atresia. Am J Physiol Gastrointest Liver Physiol 309:G466–G474

    Article  CAS  Google Scholar 

  25. Riepenhoff-Talty M, Schaekel K et al (1993) Group A rotaviruses produce extrahepatic biliary obstruction in orally inoculated newborn mice. Pediatr Res 33:394–399

    CAS  Google Scholar 

  26. Petersen C, Grasshoff S, Luciano L (1998) Diverse morphology of biliary atresia in an animal model. J Hepatol 28:603–607

    Article  CAS  Google Scholar 

  27. Czech-Schmidt G, Verhagen W, Szavay P et al (2001) Immunological gap in the infectious animal model for biliary atresia. J Surg Res 101:62–67

    Article  CAS  Google Scholar 

  28. Mohanty SK, Donnelly B, Bondoc A et al (2013) Rotavirus replication in the cholangiocyte mediates the temporal dependence of murine biliary atresia. PLoS One 8:e69069

    Article  CAS  Google Scholar 

  29. Jafri M, Donnelly B, McNeal M et al (2007) MAPK signaling contributes to rotaviral-induced cholangiocyte injury and viral replication. Surgery 142:192–201

    Article  Google Scholar 

  30. Jafri M, Donnelly B, Bondoc A et al (2009) Cholangiocyte secretion of chemokines in experimental biliary atresia. J Pediatr Surg 44:500–507

    Article  Google Scholar 

  31. Mohanty SK, Donnelly B, Lobeck I et al (2017) The SRL peptide of rhesus rotavirus VP4 protein governs cholangiocyte infection and the murine model of biliary atresia. Hepatology 65:1278–1292

    Article  CAS  Google Scholar 

  32. Allen SR, Jafri M, Donnelly B et al (2007) Effect of rotavirus strain on the murine model of biliary atresia. J Virol 81:1671–1679

    Article  CAS  Google Scholar 

  33. Wang W, Donnelly B, Bondoc A et al (2011) The rhesus rotavirus gene encoding VP4 is a major determinant in the pathogenesis of biliary atresia in newborn mice. J Virol 85:9069–9077

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the grants funded by National Institutes of Health (NIH) grant R01 DK-091566.

Author information

Authors and Affiliations

  1. Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Centre, Cincinnati, OH, USA

    Sujit K. Mohanty, Bryan Donnelly, Haley Temple & Gregory M. Tiao

Authors
  1. Sujit K. Mohanty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bryan Donnelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haley Temple
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregory M. Tiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregory M. Tiao .

Editor information

Editors and Affiliations

  1. Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels, Belgium

    Mathieu Vinken

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Mohanty, S.K., Donnelly, B., Temple, H., Tiao, G.M. (2019). A Rotavirus-Induced Mouse Model to Study Biliary Atresia and Neonatal Cholestasis. In: Vinken, M. (eds) Experimental Cholestasis Research. Methods in Molecular Biology, vol 1981. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9420-5_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9420-5_17

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9419-9

  • Online ISBN: 978-1-4939-9420-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation