pp59fyn Mutant Mice Display Differential Signaling in Thymocytes and Peripheral T Cells

Cell. 1992 Sep 4;70(5):741-50. doi: 10.1016/0092-8674(92)90308-y.

Abstract

We have generated mutant mice that do not express pp59fyn, a nonreceptor protein tyrosine kinase related to pp60src, by homologous recombination in embryonic stem cells. fyn- mice did not display an overt phenotype. Because fyn is associated with the T cell receptor (TCR), thymocyte and T cell signaling was analyzed in the mutant background. Cross-linking of TCR-CD3 in thymocytes led to markedly reduced calcium fluxes and abrogated proliferation, whereas mature splenic T cells retained largely normal proliferation despite depressed calcium movements and IL-2 production. Similarly, proliferation induced by Thy-1 cross-linking was reduced in thymocytes but not in splenic T cells. fyn- thymocytes were impaired at a late stage of maturation and showed limited clonal deletion to the Mls-1a self-super-antigen but not to staphylococcal enterotoxin A. These results implicate fyn as a critical component in TCR signaling in thymocytes and, potentially, in the process that determines T cell repertoire in the adult mouse.

Publication types

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

MeSH terms

  • Animals
  • Antibodies
  • Antigens, Differentiation, T-Lymphocyte
  • Base Sequence
  • CD3 Complex
  • Cell Differentiation
  • Cells, Cultured
  • Ionomycin
  • Lymphocyte Activation*
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Phorbol Esters
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-fyn
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction*
  • T-Lymphocytes / physiology*
  • Thymus Gland / cytology
  • Thymus Gland / ultrastructure

Substances

  • Antibodies
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Phorbol Esters
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • Ionomycin
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn