The Cd48 gene, also know as Slamf2 (signaling lymphocytic activation molecule 2), encodes for a lymphocyte cell surface antigen that binds CD2 and CD244 and is involved in regulation of T cell activation. These mice carry a targeted mutation for Cd48, in which a NEO cassette has replaced the exon encoding the immunoglobulin-V-like domain (the binding domain for CD2). Mice that are homozygous for the targeted mutation are viable and fertile. No cell surface CD48 protein is detected by flow cytometric analysis of thymocytes and splenocytes from homozygous animals. Female homozygotes develop auto-antibodies by 3 months, and glomerulonephritis by 6 months of age. Homozygotes exhibit increased numbers of short term hematopoietic stem cells (HSC) and multipotent progenitor cells, while decreased numbers of myeloid progenitor cells. HSCs from homozygotes have impaired short term engraftment in transplantation studies, as well as defective proliferation (increased quiescence). Cytokine and interferon gamma levels in the bone marrow of homozygotes are significantly reduced. Homozygotes on the congenic C57BL/6 background have a shortened lifespan (most die by 80 weeks of age) compared to wildtype controls. By approximately 16 weeks of age, most homozygotes have developed tumors (predominantly lymphomas)