An activated lck transgene promotes thymocyte development in RAG-1 mutant mice.
Expression of the T cell receptor beta (TCR beta) chain is necessary for the transition from the CD4CD8- stage in the major alpha beta thymocyte lineage. The protein tyrosine kinase p56lck has been implicated in the regulation of early thymocyte differentiation and of allelic exclusion at the TCR beta locus. Using mice overexpressing an activated lck transgene and mice with a disruption of the lck gene, we demonstrate that p56lck participates in a pathway that regulates the expansion of the pool of CD4+CD8+ thymocytes to wild-type levels. In addition, p56lck may be involved in the down-regulation of the putative pre-TCR on CD4+CD8+ thymocytes.
Mombaerts
P
P
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Anderson
S J
SJ
Perlmutter
R M
RM
Mak
T W
TW
Tonegawa
S
S
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology
D015704:CD4 Antigens; D016827:CD8 Antigens; D018398:Homeodomain Proteins; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)