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Molecular and Cellular Biology, July 2004, p. 6067-6075, Vol. 24, No. 13
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.13.6067-6075.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Immune Functions in Mice Lacking Clnk, an SLP-76-Related Adaptor Expressed in a Subset of Immune Cells

Oliver Utting,1 Bradley J. Sedgmen,2 Tania H. Watts,2 Xiaoshu Shi,1 Robert Rottapel,3 Angelo Iulianella,4,5 David Lohnes,4,5 and André Veillette1,5,6*

Laboratory of Molecular Oncology,1 Laboratory of Molecular and Cellular Biology, Clinical Research Institute of Montreal, Montréal, Québec, Canada H2W 1R7,4 Department of Immunology, University of Toronto, Toronto, Ontario, Canada M5S 1A8,2 Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2C1,3 Departments of Microbiology and Immunology,6 Medicine, McGill University, Montréal, Québec, Canada H3G 1Y65

Received 20 February 2004/ Returned for modification 3 April 2004/ Accepted 9 April 2004

The SLP-76 family of immune cell-specific adaptors is composed of three distinct members named SLP-76, Blnk, and Clnk. They have been implicated in the signaling pathways coupled to immunoreceptors such as the antigen receptors and Fc receptors. Previous studies using gene-targeted mice and deficient cell lines showed that SLP-76 plays a central role in T-cell development and activation. Moreover, it is essential for normal mast cell and platelet activation. In contrast, Blnk is necessary for B-cell development and activation. While the precise function of Clnk is not known, it was reported that Clnk is selectively expressed in mast cells, natural killer (NK) cells, and previously activated T-cells. Moreover, ectopic expression of Clnk was shown to rescue T-cell receptor-mediated signal transduction in an SLP-76-deficient T-cell line, suggesting that, like its relatives, Clnk is involved in the positive regulation of immunoreceptor signaling. Stimulatory effects of Clnk on immunoreceptor signaling were also reported to occur in transfected B-cell and basophil leukemia cell lines. Herein, we attempted to address the physiological role of Clnk in immune cells by the generation of Clnk-deficient mice. The results of our studies demonstrated that Clnk is dispensable for normal differentiation and function of T cells, mast cells, and NK cells. Hence, unlike its relatives, Clnk is not essential for normal immune functions.

* Corresponding author. Mailing address: IRCM, 110 Pine Ave. West, Montreal, Quebec, Canada H2W 1R7. Phone: (514) 987-5561. Fax: (514) 987-5562. E-mail: veillea{at}ircm.qc.ca.

Molecular and Cellular Biology, July 2004, p. 6067-6075, Vol. 24, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.13.6067-6075.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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