Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-5-8
pubmed:abstractText
Autoimmune hepatitis (AIH) in humans arises spontaneously in genetically susceptible individuals and is associated with the presence of Th1 cells in the liver. The understanding of AIH has advanced more slowly than that of other organ-specific autoimmune diseases, however, largely because of the lack of an appropriate animal model. We now describe a new mouse model characterized by spontaneous development of necroinflammatory hepatitis that is restricted by genetic background. Mice deficient in the immunomodulatory cytokine TGF-beta1 were extensively back-bred to the BALB/c background. The BALB/c background dramatically modified the phenotype of TGF-beta1(-/-) mice: specifically, BALB/c-TGF-beta1(-/-) mice developed a lethal necroinflammatory hepatitis that was not observed in TGF-beta1(-/-) mice on a different genetic background. BALB/c background TGF-beta1(-/-) livers contained large numbers of activated CD4(+) T cells that produced large quantities of IFN-gamma, but little IL-4, identifying them as Th1 cells. BALB/c background TGF-beta1(-/-)/IFN-gamma(-/-) double knockout mice, generated by cross-breeding, did not develop necroinflammatory hepatitis, demonstrating that IFN-gamma is mechanistically required for its pathogenesis. This represents the first murine model of hepatitis that develops spontaneously, is restricted by genetic background, and is dependent upon the Th1 cytokine IFN-gamma, and that thus recapitulates these important aspects of AIH.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6413-22
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11342667-Animals, pubmed-meshheading:11342667-Autoimmune Diseases, pubmed-meshheading:11342667-Cell Differentiation, pubmed-meshheading:11342667-Crosses, Genetic, pubmed-meshheading:11342667-Genetic Predisposition to Disease, pubmed-meshheading:11342667-Hepatitis, Animal, pubmed-meshheading:11342667-Interferon-gamma, pubmed-meshheading:11342667-Liver, pubmed-meshheading:11342667-Mice, pubmed-meshheading:11342667-Mice, Inbred BALB C, pubmed-meshheading:11342667-Mice, Inbred C57BL, pubmed-meshheading:11342667-Mice, Inbred Strains, pubmed-meshheading:11342667-Mice, Knockout, pubmed-meshheading:11342667-Necrosis, pubmed-meshheading:11342667-Survival Rate, pubmed-meshheading:11342667-Th1 Cells, pubmed-meshheading:11342667-Th2 Cells, pubmed-meshheading:11342667-Transforming Growth Factor beta, pubmed-meshheading:11342667-Transforming Growth Factor beta1
pubmed:year
2001
pubmed:articleTitle
Genetic regulation of autoimmune disease: BALB/c background TGF-beta 1-deficient mice develop necroinflammatory IFN-gamma-dependent hepatitis.
pubmed:affiliation
Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756, USA. James.D.Gorham@Dartmouth.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't