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

摘要: NK cells are implicated in antiviral responses, bone marrow transplantation and tumor immunosurveillance. Their function is controlled, part, through the Ly49 family of class I binding receptors. Inhibitory Ly49s suppress signaling, while activating (i.e., Ly49D) activate via DAP12 signaling chain. Activating has been studied primarily C57BL/6 mice, however, 129 substrains commonly used gene-targeting experiments. In this study, we show that contrast to cells, cross-linking DAP12-coupled receptors 129/J mice induces phosphorylation but not calcium mobilization or cytokine production. Consistent with poor-activating function, reject less efficiently than mice. Sequence analysis suggests no structural basis for inactivity, both demonstrate normal a reconstituted receptor system. Most importantly, reconstitution Ly49D demonstrated deficit within themselves. These unexpected findings bring into question any 129/J, 129Sv, gene-targeted derived from these strains before complete backcrossing, provide possible explanation differences observed immune response variety models.