We have created embryonic stem (ES) cells and mice lacking the predominant isoform (alpha) of the calcineurin A subunit (CNA alpha) to study the role of this serine/threonine phosphatase in the immune system. T and B cell maturation appeared to be normal in CNA alpha -/- mice. CNA alpha -/- T cells responded normally to mitogenic stimulation (i.e., PMA plus ionomycin, concanavalin A, and anti-CD3 epsilon antibody). However, CNA alpha -/- mice generated defective antigen-specific T cell responses in vivo. Mice produced from CNA alpha -/- ES cells injected into RAG-2-deficient blastocysts had a similar defective T cell response, indicating that CNA alpha is required for T cell function per se, rather than for an activity of other cell types involved in the immune response. CNA alpha -/- T cells remained sensitive to both cyclosporin A and FK506, suggesting that CNA beta or another CNA-like molecule can mediate the action of these immunosuppressive drugs. CNA alpha -/- mice provide an animal model for dissecting the physiologic functions of calcineurin as well as the effects of FK506 and CsA.
T cell responses in calcineurin A alpha-deficient mice.
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B W Zhang, G Zimmer, J Chen, D Ladd, E Li, F W Alt, G Wiederrecht, J Cryan, E A O'Neill, C E Seidman, A K Abbas, J G Seidman; T cell responses in calcineurin A alpha-deficient mice.. J Exp Med 1 February 1996; 183 (2): 413–420. doi: https://doi.org/10.1084/jem.183.2.413
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