Profound Block in Thymocyte Development in Mice Lacking p56(lck)

• Published in: Nature (London) Vol. 357; no. 6374; p. 161
• Main Authors: Molina, T J, Kishihara, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 14.05.1992
• Subjects: Cellular biology; Glycoproteins; Mutation; Stem cells
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/357161a0

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.