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• W1981741977 abstract "Summary Loss of ζ ‐associated protein 70 (Zap70) results in severe immunodeficiency in humans and mice because of the critical role of Zap70 in T‐cell receptor ( TCR ) signalling. Here we describe a novel mouse strain generated by N ‐ethyl‐ N ‐nitrosourea mutagenesis, with the reduced protein stability ( rps ) mutation in Zap70 . The A243V rps mutation resulted in decreased Zap70 protein and a reduced duration of TCR ‐induced calcium responses, equivalent to that induced by a 50% decrease in catalytically active Zap70. The reduction of signalling through Zap70 was insufficient to substantially perturb thymic differentiation of conventional CD 4 and CD 8 T cells, although Foxp3 + regulatory T cells demonstrated altered thymic production and peripheral homeostasis. Despite the mild phenotype, the Zap70 A243V variant lies just above the functional threshold for TCR signalling competence, as T cells relying on only a single copy of the Zap70 rps allele for TCR signalling demonstrated no intracellular calcium response to TCR stimulation. This addition to the Zap70 allelic series indicates that a rate‐limiting threshold for Zap70 protein levels exists at which signalling capacity switches from nearly intact to effectively null." @default.
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• W1981741977 date "2014-02-10" @default.
• W1981741977 modified "2023-10-04" @default.
• W1981741977 title "A novel Zap70 mutation with reduced protein stability demonstrates the rate-limiting threshold for Zap70 in T-cell receptor signalling" @default.
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• W1981741977 doi "https://doi.org/10.1111/imm.12199" @default.
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