T cell receptor delta gene mutant mice: independent generation of alpha beta T cells and programmed rearrangements of gamma delta TCR genes.
T cells bearing T cell receptor (TCR) gamma and delta chain heterodimers are first generated early in ontogeny. They form distinct subsets that differ in their TCR repertoires and tissue distribution. Disruption of the mouse TCR C delta gene segment by a gene targeting method caused the complete loss of T cells bearing TCR gamma delta chains, but had little or no effect on the development of T cells bearing TCR alpha beta chains. The analyses of TCR gamma and delta genes in the mutant mice suggest that intracellular mechanisms acting at the level of DNA rearrangement play key roles in the differential gamma and delta gene rearrangements and in the generation of the highly restricted junctional sequences during fetal thymic development.
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139.
S
S
Itohara
P
P
Mombaerts
J
J
Lafaille
J
J
Iacomini
A
A
Nelson
A R
AR
Clarke
M L
ML
Hooper
A
A
Farr
S
S
Tonegawa
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002678:Chimera; D003713:Dendritic Cells / Q000166:cytology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D005434:Flow Cytometry; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D015183:Restriction Mapping; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology
D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta