TCR selection and allelic exclusion in RAG transgenic mice that exhibit abnormal T cell localization in lymph nodes and lymphatics.
RAG-1 and RAG-2 are developmentally regulated genes that are essential for V(D)J recombination and lymphocyte development. Expression of RAG-1 and RAG-2 by thymocytes is normally limited to cells that have not completed selection. We have previously documented that persistent expression of the recombinase activating genes (RAG) in transgenic mice results in aberrant thymic development, altered lymphatic microanatomy, and a profound immunodeficiency. Here we further document the pathologic changes found in TG.RAG-1,2 mice and examine the role of TCR recombination and positive and negative thymic selection, as well as allelic exclusion, in the etiology of the phenotype. We find that neither selection nor TCR allelic exclusion can be overcome by transgenic expression RAG-1 and RAG-2 under the control of an lck promoter.
Wayne
J
J
Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021.
Suh
H
H
Sokol
K A
KA
Petrie
H T
HT
Witmer-Pack
M
M
Edelhoff
S
S
Disteche
C M
CM
Nussenzweig
M C
MC
D000483:Alleles; D000818:Animals; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D018398:Homeodomain Proteins; D008099:Liver / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D008208:Lymphatic System / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011506:Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein