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

Abstract

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.

We thank Jie Yu for generating the targeting vector and Catherine Riou for screening the ES clones. We also thank Sylvain Latour for providing RMA and RMA-S cells and Andrew Makrigiannis for help with NK cell cultures.

This work was supported by grants from the National Cancer Institute of Canada (to A.V.) and the Canadian Institutes of Health Research (to A.V., T.H.W., and D.L.). O.U. holds a Fellowship from the Canadian Institutes of Health Research. A.V. is recipient of the Canada Research Chair in Immune Cell Signaling and is a Senior Scientist of the Canadian Institutes of Health Research.