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Profound block in thymocyte development in mice lacking p56lck.

The protein Lck (p56lck) has a relative molecular mass of 56,000 and belongs to the Src family of tyrosine kinases. It is expressed exclusively in lymphoid cells, predominantly in thymocytes and peripheral T cells. Lck associates specifically with the cytoplasmic domains of both CD4 and CD8 T-cell surface glycoproteins and interacts with the beta-chain of the interleukin-2 receptor, which implicates Lck activity in signal transduction during thymocyte ontogeny and activation of mature T cells. Here we generate an lck null mutation by homologous recombination in embryonic stem cells to evaluate the role of p56lck in T-cell development and activation. Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. Mature, single-positive thymocytes are not detectable in these mice and there are only very few peripheral T cells. These results illustrate the crucial role of this T-cell-specific tyrosine kinase in the thymocyte development.

Pubmed ID: 1579166

Authors

  • Molina TJ
  • Kishihara K
  • Siderovski DP
  • van Ewijk W
  • Narendran A
  • Timms E
  • Wakeham A
  • Paige CJ
  • Hartmann KU
  • Veillette A

Journal

Nature

Publication Data

May 14, 1992

Associated Grants

None

Mesh Terms

  • Animals
  • Antisense Elements (Genetics)
  • B-Lymphocytes
  • Base Sequence
  • Heterozygote
  • Immunoglobulins
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Oligodeoxyribonucleotides
  • Protein-Tyrosine Kinases
  • T-Lymphocyte Subsets
  • T-Lymphocytes