Impaired Viability and Profound Block in Thymocyte Development in Mice Lacking the Adaptor Protein SLP-76

• Published in: Cell 1998-07, Vol.94 (2), p.229-238
• Main Authors: Pivniouk, Vadim, Tsitsikov, Erdyni, Swinton, Paul, Rathbun, Gary, Alt, Frederick W, Geha, Raif S
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Animals; Antigens, CD - analysis; Bone Marrow Cells; CD3 Complex - physiology; Cell Differentiation; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor - genetics; Killer Cells, Natural; Macrophages; Mice; Mice, Knockout; Phosphoproteins - genetics; Phosphoproteins - physiology; Receptors, Antigen, T-Cell, gamma-delta - analysis; Spleen - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymus Gland - growth & development; Thymus Gland - immunology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)81422-1

The adaptor protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation. SLP-76-deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4 +8 + thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCRβ locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes.