Authors: | Wayne, J.; Suh, H.; Sokol, K. A.; Petrie, H. T.; Witmer-Pack, M.; Edelhoff, S.; Disteche, C. M.; Nussenzweig, M. C. |
Article Title: | TCR selection and allelic exclusion in RAG transgenic mice that exhibit abnormal T cell localization in lymph nodes and lymphatics |
Abstract: | 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. |
Keywords: | controlled study; dna-binding proteins; nonhuman; flow cytometry; lymph nodes; t-lymphocytes; proteins; animal cell; mouse; phenotype; animals; mice; allele; animal tissue; spleen; alleles; gene product; homeodomain proteins; transgenic mouse; mice, transgenic; lymphatic system; gene expression regulation; gene activation; lymphocyte differentiation; t lymphocyte receptor; liver; gene rearrangement; thymus; thymus gland; lymph node; protein biosynthesis; immune deficiency; recombinase; male; female; priority journal; article; gene rearrangement, alpha-chain t-cell antigen receptor |
Journal Title: | Journal of Immunology |
Volume: | 153 |
Issue: | 12 |
ISSN: | 0022-1767 |
Publisher: | The American Association of Immunologists, Inc |
Date Published: | 1994-12-15 |
Start Page: | 5491 |
End Page: | 5502 |
Language: | English |
PROVIDER: | scopus |
PUBMED: | 7989751 |
DOI/URL: | |
Notes: | Article -- Source: Scopus |