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.
Molina
T J
TJ
Ontario Cancer Institute, University of Toronto, Canada.
Kishihara
K
K
Siderovski
D P
DP
van Ewijk
W
W
Narendran
A
A
Timms
E
E
Wakeham
A
A
Paige
C J
CJ
Hartmann
K U
KU
Veillette
A
A
D000818:Animals; D016375:Antisense Elements (Genetics); D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D006579:Heterozygote; D007136:Immunoglobulins / Q000032:analysis; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016375:Antisense Elements (Genetics); D007136:Immunoglobulins; D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)