Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76

Cell. 1998 Jul 24;94(2):229-38. 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 TCRbeta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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


  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • CD3 Complex
  • Phosphoproteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • SLP-76 signal Transducing adaptor proteins