Nomenclature: B6.129-Sh2d1a^tm1Pls

The signaling lymphocyte activation protein (SLAM) is an immunomodulatory receptor involved in regulating lymphocyte interactions and adhesion. The SLAM-associated protein (SAP) is required for SLAM signal mediation. SAP has been linked to the development of innate-like T cell lineages. SAP has also been shown to have an important role in the interactions between B cells and T cells that are instrumental in germinal center formation and long term humoral immunity. T cells lacking SAP do not maintain long-lasting interactions with B cells carrying antigens that would normally be recognized by the T cells. This observation likely explains the basis for many features of the disease known as XLP since individuals that are affected by XLP lack the SAP protein, fail to kill EBV-infected B cells and do not have germinal centers. The SAP-deficient mouse model recapitulates several features of XLP: hyperproliferative T cell response following infections, impaired NK and CD8 cell cytotoxicity, defective humoral immune responses, abnormal germinal center formation, reduction in IgG+ memory B cell numbers, and the absence of NKT and other innate T cells. It has been extensively used for studying germinal center responses and for analyses of innate T cell development. SAP protein is not present in these mice. The Sh2d1a gene is located on the X chromosome, so female knockouts are homozygous and male knockouts are hemizygous.