TY - JOUR
T1 - PanR1, a dominant negative missense allele of the gene encoding TNF-α (Tnf), does not impair lymphoid development
AU - Rutschmann, Sophie
AU - Hoebe, Kasper
AU - Zalevsky, Jonathan
AU - Du, Xin
AU - Mann, Navjiwan
AU - Dahiyat, Bassil I.
AU - Steed, Paul
AU - Beutler, Bruce
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2006/6/15
Y1 - 2006/6/15
N2 - A dominant hypomorphic allele of Tnf, PanR1, was identified in a population of G1 mice born to N-ethyl-N-nitrosourea-mutagenized sires. Macrophages from homozygotes produced no detectable TNF bioactivity, although normal quantities of immunoreactive TNF were secreted. The phenotype was confined to a critical region on mouse chromosome 17, and then ascribed to a C→A transversion at position 3480 of the Tnf gene, corresponding to the amino acid substitution P138T. As a result of subunit exchange, the protein exerts a dominant-negative effect on normal TNF trimers, interfering with the trimer/receptor interaction. Homozygotes are highly susceptible to infection by Listeria monocytogenes, confirming the essential role of TNF in innate immune defense. However, PanR1 mutant mice show normal architecture of the spleen and Peyer's patches, suggesting that TNF is not essential for the formation of these lymphoid structures.
AB - A dominant hypomorphic allele of Tnf, PanR1, was identified in a population of G1 mice born to N-ethyl-N-nitrosourea-mutagenized sires. Macrophages from homozygotes produced no detectable TNF bioactivity, although normal quantities of immunoreactive TNF were secreted. The phenotype was confined to a critical region on mouse chromosome 17, and then ascribed to a C→A transversion at position 3480 of the Tnf gene, corresponding to the amino acid substitution P138T. As a result of subunit exchange, the protein exerts a dominant-negative effect on normal TNF trimers, interfering with the trimer/receptor interaction. Homozygotes are highly susceptible to infection by Listeria monocytogenes, confirming the essential role of TNF in innate immune defense. However, PanR1 mutant mice show normal architecture of the spleen and Peyer's patches, suggesting that TNF is not essential for the formation of these lymphoid structures.
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U2 - 10.4049/jimmunol.176.12.7525
DO - 10.4049/jimmunol.176.12.7525
M3 - Article
C2 - 16751399
AN - SCOPUS:33744924870
SN - 0022-1767
VL - 176
SP - 7525
EP - 7532
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -