Hair loss and defective T- and B-cell function in mice lacking ORAI1
Authors
Gwack, YousangSrikanth, Sonal
Oh-Hora, Masatsugu
Hogan, Patrick G.
Lamperti, Edward D.
Yamashita, Megumi
Gelinas, Curtis
Neems, Daniel S.
Sasaki, Yoshiteru
Feske, Stefan
Prakriya, Murali
Rajewsky, Klaus
Rao, Anjana
Document Type
Journal ArticlePublication Date
2008-07-02Keywords
Animals; B-Lymphocytes; Calcium Channels; Calcium Signaling; Cell Differentiation; Cell Proliferation; Cytokines; Epidermis; Fibroblasts; Hair; Ion Channel Gating; Lymphocyte Subsets; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Phenotype; T-LymphocytesLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Mol Cell Biol. 2008 Sep;28(17):5209-22. Epub 2008 Jun 30. Link to article on publisher's siteDOI
10.1128/MCB.00360-08Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32977PubMed ID
18591248Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/MCB.00360-08