title: Interferon induction of (2'-5') oligoisoadenylate synthetase in diploid and trisomy 21 human fibroblasts: relation to dosage of the interferon receptor gene (IRFC).
abstract: Trisomy 21 human fibroblasts are more sensitive to human interferon-alpha (IFN-alpha) than are diploid controls, consistent with the location of the gene (IFRC) which codes for the IFN-alpha receptor on chromosome 21. When compared in the antiviral assay, the difference in sensitivity is five- to tenfold, much greater than the 50% difference in IFRC gene dosage. An understanding of the mechanism by which this amplification of gene dosage occurs is relevant to the specific pathology of Down's syndrome and as a model system for studying the pathogenic effects of chromosomal aneuploidy. The enzyme (2'-5') oligoisoadenylate synthetase (2-5A synthetase), which is believed to be central to the interferon-induced antiviral response, is induced 50% more in trisomy 21 fibroblasts than in diploid controls. Thus the amplification in response occurs subsequent to the binding of IFN-alpha to its receptor and the triggering of the first set of intracellular events, the latter exemplified by the induction of 2-5A synthetase. Similar results were obtained with IFN-gamma, consistent with other evidence which indicates that a gene coding for a separate IFN-gamma receptor is also located on chromosome 21.
mesh_terms: D004171:Diploidy; D004314:Down Syndrome / Q000235:genetics*; D004790:Enzyme Induction; D005347:Fibroblasts / Q000648:ultrastructure; D005815:Genetic Code; D006801:Humans; D007369:Interferon Inducers; D007370:Interferon Type I / Q000494:pharmacology; D011118:Polynucleotide Ligases / Q000096:biosynthesis / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017471:Receptors, Interferon
chemical_list: D007369:Interferon Inducers; D007370:Interferon Type I; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; C021906:(2'-5')oligo-isoadenylate synthetase; D011118:Polynucleotide Ligases