title: Selective loss of type I interferon-induced STAT4 activation caused by a minisatellite insertion in mouse Stat2.
abstract: The use of murine systems to model pathogen-induced human diseases presumes that general immune mechanisms between these species are conserved. One important immunoregulatory mechanism involves linkage of innate and adaptive immunity to direct the development of T helper subsets, for example toward subset 1 (TH1) development through STAT4 activation. In analyzing type I interferon signaling, we uncovered a difference between murine and human cells which may affect how these two species control linkage between innate and adaptive immunity. We show that in humans, type I interferons induce TH1 development and can activate STAT4 by recruitment to the IFN-alpha receptor complex specifically via the carboxy-terminus of STAT2. However, the mouse Stat2 gene harbors a minisatellite insertion that has altered the carboxy-terminus and selectively disrupted its capacity to activate STAT4, but not other STATs. This defect in murine Stat2 suggests that the signals leading to STAT4 activation and TH1 development in CD4+ T cells are different between mice and humans.
authors.affiliation: Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Farrar
authors.forename: J D
authors.initials: JD
authors.lastname: Smith
authors.forename: T L
authors.initials: TL
authors.lastname: Murphy
authors.forename: S
authors.initials: S
authors.lastname: Leung
authors.forename: G R
authors.initials: GR
authors.lastname: Stark
authors.forename: K M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D050795:STAT2 Transcription Factor; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C494085:Stat2 protein, mouse; C494091:Stat4 protein, mouse; D015534:Trans-Activators