Profound block in thymocyte development in mice lacking p56lck

T. J. Molina, K. Kishihara, D. P. Siderovskid, W. Van Ewijk, A. Narendran, E. Timms, A. Wakeham, C. J. Paige, K. U. Hartmann, A. Veillette, D. Davidson, T. W. Mak

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Abstract

THE protein Lck (p56lck) has a relative molecular mass of 56,000 and belongs to the Src family of tyrosine kinases1-3. It is expressed exclusively in lymphoid cells, predominantly in thymocytes and peripheral T cells4,5. Lck associates specifically with the cytoplasmic domains of both CD4 and CD8 T-cell surface glycoproteins 6,7 and interacts with the β-chain of the interleukin-2 receptor8, which implicates Lck activity in signal transduction during thymocyte ontogeny9-13 and activation of mature T cells 14-19. 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.

Original languageEnglish
Pages (from-to)161-164
Number of pages4
JournalNature
Volume357
Issue number6374
DOIs
StatePublished - 1 Jan 1992

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    Molina, T. J., Kishihara, K., Siderovskid, D. P., Van Ewijk, W., Narendran, A., Timms, E., Wakeham, A., Paige, C. J., Hartmann, K. U., Veillette, A., Davidson, D., & Mak, T. W. (1992). Profound block in thymocyte development in mice lacking p56lck. Nature, 357(6374), 161-164. https://doi.org/10.1038/357161a0