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

Yousang Gwack, Sonal Srikanth, Masatsugu Oh-hora, Patrick G. Hogan, Edward D. Lamperti, Megumi Yamashita, Curtis Gelinas, Daniel S. Neems, Yoshiteru Sasaki, Stefan Feske, Murali Prakriya, Klaus Rajewsky, Anjana Rao

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    221 Citations (Scopus)

    Abstract

    ORAI1 is a pore subunit of the store-operated Ca2+ release-activated Ca2+ (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-speciflc deletion of the Cnb1 gene. T and B cells developed normally in Orai1-/- mice, but B cells showed a substantial decrease in Ca2+ influx and cell proliferation in response to B-cell receptor stimulation. Naïve and differentiated Orai1-/- T cells showed substantial reductions in store-operated Ca2+ 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.

    Original languageEnglish
    Pages (from-to)5209-5222
    Number of pages14
    JournalMolecular and cellular biology
    Volume28
    Issue number17
    DOIs
    Publication statusPublished - Sep 2008

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Cell Biology

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