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Science 27 August 1993:
Vol. 261. no. 5125, pp. 1175 - 1178
DOI: 10.1126/science.8356452

Articles

Science, Vol 261, Issue 5125, 1175-1178
Copyright © 1993 by American Association for the Advancement of Science


articles

Mice lacking TdT: mature animals with an immature lymphocyte repertoire

S Gilfillan, A Dierich, M Lemeur, C Benoist, and D Mathis

Laboratoire de Genetique Moleculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Strasbourg, France.

In adult animals, template-independent (or N) nucleotides are frequently added during the rearrangement of variable (V), diversity (D), and joining (J) segments of lymphocyte receptor genes, greatly enhancing junctional diversity. Receptor genes from adult mice carrying a mutation in the terminal deoxynucleotidyl transferase (TdT) gene have few N nucleotides, providing proof that this enzyme is essential for creating diversity. Unlike those from normal adults, receptor genes from adult mutant mice show extensive evidence of homology-directed recombination, suggesting that TdT blocks this process. Thus, switch-on of the TdT gene during the first week after birth provokes an even greater expansion of lymphocyte receptor diversity than had previously been thought.


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J. Immunol. 161, 6093-6104
   Abstract »    Full Text »    PDF »
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F. Nourrit, N. Doyen, P. Kourilsky, F. Rougeon, and A. Cumano (1998)
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   Abstract »    Full Text »    PDF »
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N. Tuaillon and J. D. Capra (1998)
PNAS 95, 1703-1708
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Long-Lived Th2 Clones Specific for Seasonal and Perennial Allergens Can Be Detected in Blood and Skin by Their TCR-Hypervariable Regions.
B. Bohle, H. Schwihla, H.-Z. Hu, R. Friedl-Hajek, S. Sowka, F. Ferreira, H. Breiteneder, C. A. F. M. Bruijnzeel-Koomen, R. A. de Weger, G. C. Mudde, et al. (1998)
J. Immunol. 160, 2022-2027
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Mycoplasma Superantigen Is a CDR3-dependent Ligand for the T Cell Antigen Receptor.
A. S. Hodtsev, Y. Choi, E. Spanopoulou, and D. N. Posnett (1998)
J. Exp. Med. 187, 319-327
   Abstract »    Full Text »    PDF »
Footprint Analysis of the RAG Protein Recombination Signal Sequence Complex for V(D)J Type Recombination.
F. Nagawa, K.-i. Ishiguro, A. Tsuboi, T. Yoshida, A. Ishikawa, T. Takemori, A. J. Otsuka, and H. Sakano (1998)
Mol. Cell. Biol. 18, 655-663
   Abstract »    Full Text »
Double Strand Break Repair.
G. Chu (1997)
J. Biol. Chem. 272, 24097-24100
   Full Text »    PDF »
In vitro V(D)J recombination: Signal joint formation.
P. Cortes, F. Weis-Garcia, Z. Misulovin, A. Nussenzweig, J.-S. Lai, G. Li, M. C. Nussenzweig, and D. Baltimore (1996)
PNAS 93, 14008-14013
   Abstract »    Full Text »    PDF »
Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line.
S. Lees-Miller, R Godbout, D. Chan, M Weinfeld, R. Day 3rd, G. Barron, and J Allalunis-Turner (1995)
Science 267, 1183-1185
   Abstract »    PDF »
Rescue of T cell-specific V(D)J recombination in SCID mice by DNA-damaging agents.
J. Danska, F Pflumio, C. Williams, O Huner, J. Dick, and C. Guidos (1994)
Science 266, 450-455
   Abstract »    PDF »
Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice..
E Spanopoulou, C A Roman, L M Corcoran, M S Schlissel, D P Silver, D Nemazee, M C Nussenzweig, S A Shinton, R R Hardy, and D Baltimore (1994)
Genes & Dev. 8, 1030-1042
   Abstract »    PDF »
Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes.
T Komori, A Okada, V Stewart, and F. Alt (1993)
Science 261, 1171-1175
   Abstract »    PDF »
Comparison of the Two Murine Deoxynucleotidyltransferase Terminal Isoforms. A 20-AMINO ACID INSERTION IN THE HIGHLY CONSERVED CARBOXYL-TERMINAL REGION MODIFIES THE THERMOSENSITIVITY BUT NOT THE CATALYTIC ACTIVITY.
J.-B. Boule, F. Rougeon, and C. Papanicolaou (2000)
J. Biol. Chem. 275, 28984-28988
   Abstract »    Full Text »    PDF »
Terminal Deoxynucleotidyl Transferase Indiscriminately Incorporates Ribonucleotides and Deoxyribonucleotides.
J.-B. Boule, F. Rougeon, and C. Papanicolaou (2001)
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