Aberrant DAP12 Signaling in the 129 Strain of Mice: Implications for the Analysis of Gene-Targeted Mice Export

@article{mcvicar_aberrant_2002, abstract = {NK cells are implicated in antiviral responses, bone marrow transplantation and tumor immunosurveillance. Their function is controlled, in part, through the Ly49 family of class I binding receptors. Inhibitory Ly49s suppress signaling, while activating Ly49s (i.e., Ly49D) activate NK cells via the DAP12 signaling chain. Activating Ly49 signaling has been studied primarily in C57BL/6 mice, however, 129 substrains are commonly used in gene-targeting experiments. In this study, we show that in contrast to C57BL/6 NK cells, cross-linking of DAP12-coupled receptors in 129/J mice induces phosphorylation of DAP12 but not calcium mobilization or cytokine production. Consistent with poor-activating Ly49 function, 129/J mice reject bone marrow less efficiently than C57BL/6 mice. Sequence analysis of receptors and DAP12 suggests no structural basis for inactivity, and both the 129/J and C57BL/6 receptors demonstrate normal function in a reconstituted receptor system. Most importantly, reconstitution of Ly49D in 129/J NK cells demonstrated that the signaling deficit is within the NK cells themselves. These unexpected findings bring into question any NK analysis of 129/J, 129Sv, or gene-targeted mice derived from these strains before complete backcrossing, and provide a possible explanation for the differences observed in the immune response of 129 mice in a variety of models.}, author = {Mcvicar, Daniel W. and Pickett, Robin W. and Taylor, Lynn S. and Makrigiannis, Andrew and Bennett, Michael and Anderson, Stephen K. and Ortaldo, John R.}, citeulike-article-id = {2705513}, citeulike-linkout-0 = {http://www.jimmunol.org/cgi/content/abstract/169/4/1721}, journal = {J Immunol}, keywords = {dap12, nk}, month = {August}, pages = {1721--1728}, posted-at = {2008-04-23 05:48:26}, priority = {0}, title = {Aberrant DAP12 Signaling in the 129 Strain of Mice: Implications for the Analysis of Gene-Targeted Mice}, url = {http://www.jimmunol.org/cgi/content/abstract/169/4/1721}, volume = {169}, year = {2002} }

TY - JOUR ID - mcvicar_aberrant_2002 L3 - citeulike-article-id:2705513 N2 - NK cells are implicated in antiviral responses, bone marrow transplantation and tumor immunosurveillance. Their function is controlled, in part, through the Ly49 family of class I binding receptors. Inhibitory Ly49s suppress signaling, while activating Ly49s (i.e., Ly49D) activate NK cells via the DAP12 signaling chain. Activating Ly49 signaling has been studied primarily in C57BL/6 mice, however, 129 substrains are commonly used in gene-targeting experiments. In this study, we show that in contrast to C57BL/6 NK cells, cross-linking of DAP12-coupled receptors in 129/J mice induces phosphorylation of DAP12 but not calcium mobilization or cytokine production. Consistent with poor-activating Ly49 function, 129/J mice reject bone marrow less efficiently than C57BL/6 mice. Sequence analysis of receptors and DAP12 suggests no structural basis for inactivity, and both the 129/J and C57BL/6 receptors demonstrate normal function in a reconstituted receptor system. Most importantly, reconstitution of Ly49D in 129/J NK cells demonstrated that the signaling deficit is within the NK cells themselves. These unexpected findings bring into question any NK analysis of 129/J, 129Sv, or gene-targeted mice derived from these strains before complete backcrossing, and provide a possible explanation for the differences observed in the immune response of 129 mice in a variety of models. JF - J Immunol EP - 1728 TI - Aberrant DAP12 Signaling in the 129 Strain of Mice: Implications for the Analysis of Gene-Targeted Mice VL - 169 SP - 1721 KW - dap12 KW - nk AU - Mcvicar, Daniel AU - Pickett, Robin AU - Taylor, Lynn AU - Makrigiannis, Andrew AU - Bennett, Michael AU - Anderson, Stephen AU - Ortaldo, John PY - 2002/August// UR - http://www.jimmunol.org/cgi/content/abstract/169/4/1721 ER -