ArticleGenes and immunity2005
A new coding mutation in the Tnf-alpha leader sequence in tuberculosis-sensitive I/St mice causes higher secretion levels of soluble TNF-alpha.
Article in Genes and immunity, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 12 citations in OpenAlex.
- Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies.Seminars in immunopathology · 2016Review
- Complex genetic control of susceptibility to Mycobacterium bovis (Bacille Calmette-Guérin) infection in wild-derived Mus spretus mice.Genes and immunity · 2006Article
- Genetic architecture of tuberculosis resistance in a mouse model of infection.Genes and immunity · 2006Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
I/St and A/Sn mice are polar extremes in terms of several parameters defining sensitivity to Mycobacterium tuberculosis. TNF-alpha, mainly produced by activated macrophages, can mediate both physiological and pathophysiological processes. Adequate TNF-alpha levels are essential for a forceful protective response to M. tuberculosis. We have functionally characterized a nonsynonymous substitution, Arg8 His, in the highly conserved cytoplasmic domain of the pro-TNF-alpha leader peptide from extremely M. tuberculosis-sensitive I/St mice. This was compared to the common pro-TNF-alpha variant found in A/Sn mice. Using cDNA constructs, both variants were constitutively expressed in HEK293A cells. A significantly higher secretion level of Arg8 His TNF-alpha was shown using flow cytometry and ELISA analysis (P=0.0063), while intracellular levels were similar for both protein variants. An even TNF-alpha distribution throughout the cells was seen using confocal microscopy. This suggests that the Arg8 His substitution affects pro-TNF-alpha processing. The I/St mouse may serve as a model to further explore the function of the well-conserved cytoplasmic region of TNF-alpha. However, other identified substitutions in the I/St promoter, introns and 3'UTR of Tnf-alpha, as well as the cellular environment in vivo may affect the balance between soluble and intracellular Arg8 His TNF-alpha before and during M. tuberculosis infection.
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Registered trials
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