Title

Hair loss and defective T- and B-cell function in mice lacking ORAI1

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Pathology

Publication Date

2008-07-02

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

ORAI1 is a pore subunit of the store-operated Ca(2+) release-activated Ca(2+) (CRAC) channel. To examine the physiological consequences of ORAI1 deficiency, we generated mice with targeted disruption of the Orai1 gene. The results of immunohistochemical analysis showed that ORAI1 is expressed in lymphocytes, skin, and muscle of wild-type mice and is not expressed in Orai1(-/-) mice. Orai1(-/-) mice with the inbred C57BL/6 background showed perinatal lethality, which was overcome by crossing them to outbred ICR mice. Orai1(-/-) mice were small in size, with eyelid irritation and sporadic hair loss resembling the cyclical alopecia observed in mice with keratinocyte-specific deletion of the Cnb1 gene. T and B cells developed normally in Orai1(-/-) mice, but B cells showed a substantial decrease in Ca(2+) influx and cell proliferation in response to B-cell receptor stimulation. Naive and differentiated Orai1(-/-) T cells showed substantial reductions in store-operated Ca(2+) entry, CRAC currents, and cytokine production. These features are consistent with the severe combined immunodeficiency and mild extraimmunological symptoms observed in a patient with a missense mutation in human ORAI1 and distinguish the ORAI1-null mice described here from a previously reported Orai1 gene-trap mutant mouse which may be a hypomorph rather than a true null.

DOI of Published Version

10.1128/MCB.00360-08

Source

Mol Cell Biol. 2008 Sep;28(17):5209-22. Epub 2008 Jun 30. Link to article on publisher's site

Journal/Book/Conference Title

Molecular and cellular biology

Related Resources

Link to Article in PubMed

PubMed ID

18591248

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