| First Author | McVicar DW | Year | 2002 |
| Journal | J Immunol | Volume | 169 |
| Issue | 4 | Pages | 1721-8 |
| PubMed ID | 12165492 | Mgi Jnum | J:78244 |
| Mgi Id | MGI:2183853 | Doi | 10.4049/jimmunol.169.4.1721 |
| Citation | McVicar DW, et al. (2002) Aberrant DAP12 signaling in the 129 strain of mice: implications for the analysis of gene-targeted mice. J Immunol 169(4):1721-8 |
| abstractText | 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. |
