Springer Online Journal Archives 1860-2000
Summary Trisomy 21 human fibroblasts are more sensitive to human interferon-α (IFN-α) than are diploid controls, consistent with the location of the gene (IFRC) which codes for the IFN-α receptor on chromosome 21. When compared in the antiviral assay, the difference in sensitivity is five-to tenfold, much greater then 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-α 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-γ, consistent with other evidence which indicates that a gene coding for a separate IFN-γ receptor is also located on chromosome 21.
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