A mouse strain defective for alphabeta versus gammadelta T cell lineage commitment.
As a result of a transgene insertion and chromosomal deletion, a mutant mouse strain has been found that is defective in the lineage commitment step that produces a balance of alphabeta and gammadelta T cells. The mice produce a reduced population of alphabeta CD4 T cells and almost no alphabeta CD8 T cells. Within the CD4 and CD8 populations in the thymus there exist abnormal subsets that express the gammadelta TCR. These gammadelta TCR-expressing cells populate the peripheral lymphoid organs such that up to 75% of the CD8 T cells in the lymph nodes and spleen express a gammadelta TCR. Further analyses indicate that the regulation that prevents dual TCR expression has been impaired. The locus of insertion and deletion was mapped to chromosome 10 26 cM. We have analyzed the entire locus and, in addition, the gene expression changes in early thymocytes were analyzed by gene array technology. The analysis of this mutant strain indicates that the alphabeta versus gammadelta lineage decision can be profoundly disregulated independently of successful gene rearrangements.
Department of Biology and Cancer Center, The Howard Hughes Medical Institute, and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093, USA.
Elisabeth
E
Mertsching
Andrea L
AL
Wurster
Carol
C
Katayama
Jeffrey
J
Esko
Fred
F
Ramsdell
Jamey D
JD
Marth
Stephen M
SM
Hedrick
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D019426:Integrases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000002:abnormalities / Q000254:growth & development; D014764:Viral Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C402726:Sh2d2a protein, mouse; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases