First Author | Zhang BW | Year | 1996 |
Journal | J Exp Med | Volume | 183 |
Issue | 2 | Pages | 413-20 |
PubMed ID | 8627154 | Mgi Jnum | J:71750 |
Mgi Id | MGI:2150686 | Doi | 10.1084/jem.183.2.413 |
Citation | Zhang BW, et al. (1996) T cell responses in calcineurin A alpha-deficient mice. J Exp Med 183(2):413-20 |
abstractText | 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. |