Expression of the p56(Lck) Y505F mutation in CD45-deficient mice rescues thymocyte development

Mol Cell Biol. 1999 Jun;19(6):4200-8. doi: 10.1128/MCB.19.6.4200.


Mice deficient in the transmembrane protein tyrosine phosphatase CD45 exhibit a block in thymocyte development. To determine whether the block in thymocyte development was due to the inability to dephosphorylate the inhibitory phosphorylation site (Y505) in p56(lck) (Lck), we generated CD45-deficient mice that express transgenes for the Lck Y505F mutation and the DO11.10 T-cell antigen receptor (TCR). CD4 single-positive T cells developed and accumulated in the periphery. Treatment with antigen resulted in thymocyte apoptosis and the loss of transgenic-TCR-bearing cells. Peripheral CD45-deficient T cells from the mice expressing both transgenes responded to antigen by increasing CD69 expression, interleukin-2 production, and proliferation. These results indicate that thymocyte development requires the dephosphorylation of the inhibitory site in Lck by CD45.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Crosses, Genetic
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Gene Expression Regulation
  • Immunoblotting
  • Leukocyte Common Antigens / physiology*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics*
  • Mice
  • Mice, Transgenic
  • Phosphotransferases / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins
  • Spleen / metabolism
  • Thymus Gland / growth & development*
  • Time Factors


  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Phosphotransferases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Leukocyte Common Antigens