Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels
Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels
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DOI：
10.1038/ni1550
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发表时间：
2008-01-01
影响因子：
30.5
通讯作者：
Kinet, Jean-Pierre
中科院分区：
文献类型：
--
作者：
Vig, Monika;DeHaven, Wayne I.;Kinet, Jean-Pierre
CRACM1(也称为Orai1)构成了钙释放激活的钙通道的孔亚基。CRACM1编码基因的点突变与人类严重的联合免疫缺陷疾病有关。在这里，我们产生了CRACM1缺陷小鼠，在其中P-半乳糖苷酶活性‘报告’CRACM1表达。CRACM1基因缺陷的小鼠体型较小。CRACM1基因缺陷小鼠的肥大细胞脱颗粒和细胞因子分泌存在严重缺陷，体内诱发的过敏反应在CRACM1基因缺陷小鼠中受到抑制。我们检测到CRACM1在骨骼肌以及脑、心脏和肾脏的一些区域表达旺盛，但在胸腺和脾的淋巴区域没有表达。相反，我们发现CRACM2在小鼠T细胞中的表达要高得多。与这些发现一致的是，商店操作的钙内流以及CRACM1缺陷T细胞的发育和增殖没有受到影响。因此，CRACM1在小鼠肥大细胞效应器功能中是至关重要的，但在缺少CRACM1的情况下，小鼠T细胞钙释放激活的钙通道是起作用的。
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 P-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.