Generation of a mouse model of T-cell lymphoma based on chronic LPS challenge and TGF-β signaling disruption

Nina M. Muñoz, Lior H. Katz, Ji Hyun Shin, Young Jin Gi, Vipin Kumar Menon, Mihai Gagea, Asif Rashid, Jian Chen, Lopa Mishra

Research output: Contribution to journalArticlepeer-review

Abstract

Alcoholic liver disease has various manifestations: asymptomatic steatosis, alcoholic hepatitis and alcoholic cirrhosis, conditions that substantially increase the risk for developing hepatocellular carcinoma(HCC). The Transforming Growth Factor-β (TGF-β) signaling pathway is a major regulator in chronic liver diseases contributing to liver disease progression from liver injury, inflammation and fibrosis to HCC. With the aim of generating a mouse model of alcoholic liver disease that would rapidly develop steatosis, inflammation as well as fibrosis, we formulated a regimen that combined chronic injections of low dose (2mg/kg) lipopolysaccharide (LPS) with Lieber DeCarlibased diet containing 6.7% ethanol feeding to mice with impaired TGF-β signaling through constitutive disruption of β2-spectrin and/or Smad3. Unexpectedly, the mice treated with chronic low dose LPS and fed the alcohol-containing diet developed very aggressive T-cell lymphomas to which the TGF-β mutant mice succumbed more rapidly than the wild type mice. In contrast, their liver phenotype was mild as they only developed steatosis but not hepatitis or significant fibrosis. To our knowledge, this is the first report of a mouse model of aggressive T- cell lymphoma based on chronic challenge with low dose LPS and TGF-β disruption.

Original languageEnglish
Pages (from-to)348-352
Number of pages5
JournalGenes and Cancer
Volume5
Issue number9-10
StatePublished - 2014
Externally publishedYes

Keywords

  • Smad3
  • T cell lymphoma
  • TGF-β
  • β2-spectrin

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