The V-J recombination of T cell receptor-gamma genes is blocked in interleukin-7 receptor-deficient mice.
IL-7R-deficient mice have severely impaired expansion of early lymphocytes and lack gamma delta T cells. To elucidate the role of IL-7R on gamma delta T cell development, we analyzed the rearrangements of TCR-alpha, beta, gamma, and delta genes in the thymus of the IL-7R-deficient mice. Southern blot analysis with a J gamma 1 probe revealed that more than 70% of J gamma 1 and J gamma 2 alleles are recombined to form distinct V gamma 1.2-J gamma 2 and V gamma 2-J gamma 1 fragments in control mice. On the contrary, no such recombination was detected in the mutant mice. The rearrangements in the TCR-alpha, beta, and delta loci were comparably observed in control and mutant mice. PCR analysis indicated that the V-J recombination of all the V gamma genes is severely hampered in the mutant mice. The mRNA of RAG-1, RAG-2, Ku-80, and terminal deoxynucleotidyl transferase (TdT) genes was equally detected between control and mutant thymi, suggesting that the expression of common recombination machinery is not affected. These data demonstrated that the V-J recombination of the TCR gamma genes is specifically blocked in the IL-7R-deficient mice and suggested the presence of highly specific regulation for TCR gamma gene rearrangement.
Maki
K
K
Department of Disease-related Gene Regulation Research (Sandoz), Faculty of Medicine, University of Tokyo, Japan.
Sunaga
S
S
Ikuta
K
K
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005091:Exons; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006579:Heterozygote; D018398:Homeodomain Proteins; D006720:Homozygote; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010735:Phosphoglycerate Kinase / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000235:genetics; D018123:Receptors, Interleukin / Q000378:metabolism* / Q000502:physiology; D020395:Receptors, Interleukin-7; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D017931:DNA Primers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; C499308:Rag2 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D010735:Phosphoglycerate Kinase