Description and Mapping of the Resistance of DBA/2 Mice to TNF-Induced Lethal Shock | Zendy

Ben Wielockx | Zendy; Jan Staelens | Zendy; Leen Puimège | Zendy; Ineke Vanlaere | Zendy; Maarten Van Roy | Zendy; Philippe Van Lint | Zendy; Frans van Roy | Zendy; Claude Libert | Zendy

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Description and Mapping of the Resistance of DBA/2 Mice to TNF-Induced Lethal Shock

Author(s) -

Ben Wielockx,

Jan Staelens,

Leen Puimège,

Ineke Vanlaere,

Maarten Van Roy,

Philippe Van Lint,

Frans van Roy,

Claude Libert

Publication year - 2007

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.178.8.5069

Subject(s) - tumor necrosis factor alpha , locus (genetics) , gene , biology , chromosome , genetic linkage , chromosome 4 , chromosome 9 , genetics , microbiology and biotechnology , immunology

In our search for genes that inhibit the inflammatory effects of TNF without diminishing its antitumor capacities we found that, compared with C57BL/6 mice, DBA/2 mice exhibit a dominant resistance to TNF-induced lethality. Tumor-bearing (C57BL/6 x DBA/2)(BXD)F(1) mice completely survived an otherwise lethal TNF/IFN-gamma-antitumor therapy with complete regression of the tumor. This was not the case for C57BL/6 mice. Genetic linkage analysis revealed that TNF resistance is linked to a major locus on distal chromosome 6 and a minor locus on chromosome 17. Compared with littermate controls, chromosome substitution mice carrying a DBA/2 chromosome 6 in a C57BL/6 background were significantly protected against TNF and TNF/IFN-gamma, albeit less so than DBA/2 mice. Definition of a critical region of 13 Mb on chromosome 6 was the highest mapping resolution obtained. Further analysis of candidate genes may provide a powerful tool to control TNF-induced pathologies in humans.

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