title: Analysis of interferon-gamma resistant mutants that are possibly defective in their signaling mechanism.
abstract: Our previous observations indicated that mutants partially resistant to IFN-gamma cytotoxicity were defective in the induction of indoleamine 2,3-dioxygenase, (IDO). Two mutants highly resistant to IFN-gamma were isolated following a second round of mutagenesis. The resistance to IFN-gamma was inversely correlated with the inducibility of IDO in these mutants. Moreover, several other IFN-gamma responsive genes, including those encoding 2-5A synthetase, GTP cyclohydrolase and HLA-DR alpha, were also differentially altered in their expression upon INF-gamma treatment. IFN-gamma receptor gene expression was not changed nor was the binding of the receptor to IFN-gamma. Southern blot analysis failed to reveal any significant abnormality in the IDO gene structure in these mutants. We therefore suggest that these mutants are defective in the IFN-gamma signaling pathway and will be useful in further analysis of the biochemical mechanism of IFN-gamma activated gene expression in target cells.
authors.affiliation: Department of Biology, Indiana University, Bloomington 47405.
authors.forename: G S
authors.initials: GS
authors.lastname: Feng
authors.forename: W
authors.initials: W
authors.lastname: Dai
authors.forename: S L
authors.initials: SL
authors.lastname: Gupta
authors.forename: G
authors.initials: G
authors.lastname: Werner-Felmayer
authors.forename: H
authors.initials: H
authors.lastname: Wachter
authors.forename: O
authors.initials: O
authors.lastname: Takikawa
authors.forename: M W
authors.initials: MW
authors.lastname: Taylor
mesh_terms: D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D004351:Drug Resistance / Q000235:genetics; D006136:GTP Cyclohydrolase / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D005796:Genes; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology*; D009154:Mutation; D012313:RNA / Q000235:genetics; D011971:Receptors, Immunologic / Q000378:metabolism; D017471:Receptors, Interferon; D015398:Signal Transduction; D014366:Tryptophan Oxygenase / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015342:DNA Probes; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D012313:RNA; D007371:Interferon-gamma; D004247:DNA; D014366:Tryptophan Oxygenase; D006136:GTP Cyclohydrolase