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Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels.

Abstract：

: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 beta-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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Vig M,DeHaven WI,Bird GS,Billingsley JM,Wang H,Rao PE,Hutchings AB,Jouvin MH,Putney JW,Kinet JP

doi

10.1038/ni1550

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

89-96

issue

1

eissn

1529-2908

issn

1529-2916

pii

ni1550

journal_volume

9

pub_type

杂志文章

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