CRACM1 (also called Orai1) constitutes the pore subunit of store-operated calcium release–activated calcium channels. A point mutation in the gene encoding CRACM1 is associated with severe combined immunodeficiency disease in humans. Here we generated CRACM1-deficient mice in which β-galactosidase activity 'reported' CRACM1 expression. CRACM1-deficient mice were smaller in size. Mast cells derived from CRACM1-deficient mice showed grossly defective degranulation and cytokine secretion, and the allergic reactions elicited in vivo were inhibited in CRACM1-deficient mice. We detected robust CRACM1 expression in skeletal muscles and some regions of the brain, heart and kidney but not in the lymphoid regions of thymus and spleen. In contrast, we found CRACM2 expression to be much higher in mouse T cells. In agreement with those findings, the store-operated calcium influx and development and proliferation of CRACM1-deficient T cells was unaffected. Thus, CRACM1 is crucial in mouse mast cell effector function, but mouse T cell calcium release–activated calcium channels are functional in the absence of CRACM1.
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We thank A. Dani for discussions and help with X-gal staining and analysis; M.K. Huberson for help with genotyping; B. Koller for help with the generation and analysis of in Cracm1−/− mice; and C. Bortner (National Institute of Environmental Health Sciences–National Institutes of Health, Department of Health and Human Services) for help with flow cytometry. Supported by the National Institutes of Health (GM 053950 to J.-P.K.), the Irvington Institute (M.V.) and the intramural program of the National Institutes of Health, National Institute of Environmental Health Sciences.
M.V. and J.-P.K. are consultants for Synta Pharmaceuticals.
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Vig, M., DeHaven, W., Bird, G. et al. Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release–activated calcium channels. Nat Immunol 9, 89–96 (2008). https://doi.org/10.1038/ni1550
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