Analysis of interferon-gamma resistant mutants that are possibly defective in their signaling mechanism.
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.
Feng
G S
GS
Department of Biology, Indiana University, Bloomington 47405.
Dai
W
W
Gupta
S L
SL
Werner-Felmayer
G
G
Wachter
H
H
Takikawa
O
O
Taylor
M W
MW
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
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