title: Generation of a mouse model of T-cell lymphoma based on chronic LPS challenge and TGF-β signaling disruption.
abstract: asymptomatic steatosis, alcoholic hepatitis and alcoholic cirrhosis, which substantially increase the risk for developing hepatocellular carcinoma. Transforming growth factor (TGF-β) signaling pathway is a major regulator in chronic liver diseases contributing to all 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 DeCarli-based 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.
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Muñoz
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lior H
authors.initials: LH
authors.lastname: Katz
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Shina
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Gi
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Vipin Kumar
authors.initials: VK
authors.lastname: Menon
authors.affiliation: Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gagea
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lopa
authors.initials: L
authors.lastname: Mishra
keywords: Smad3; T cell lymphoma; TGF-β; β2-spectrin