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Vol 45(2011) N 1 p. 58-65;
M.V. Korotetskaya, M.A. Kapina, M.M. Averbakh, V.V. Evstifeev, A.S. Apt*, N.N. Logunova

A Locus Involved in Tuberculosis Infection Control in Mice Locates in the Proximal Part of the H2 Complex

Central Institute of Tuberculosis, Russian Academy of Sciences, Moscow, 107564 Russia

*asapt@aha.ru
Received - 2010-07-13; Accepted - 2010-07-13

One of the genetic loci involved in tuberculosis (TB) infection control in mice is located within the chromosome 17 segment occupied by the H2 complex, the mouse MHC. Since this region spans approximately 40 Mb and contains hundreds of genes affecting immune response and host--parasite interactions, narrowing the interval by genetic recombination is necessary for identification of individual gene(s) involved. We have developed a panel of recombinant congenic mouse strains bearing different parts of the H2 complex from TB-susceptible I/St mice on the genetic background of TB-resistant C57BL/6 mice. By superposing the phenotype of severe or mild TB course of against the chart of alleles inherited by these new strains from the two parental strains, a locus involved in TB control was mapped within the segment 33.305-34.479 Mb (~1.1 Mb) of chromosome 17. Such a location indicates that allelic variants of an important proinflammatory factor TNF do not affect TB course in our experimental system. This result was confirmed by assessment of the TNF level in the lung tissue of infected mice of different strains. The QTL (quantitative trait locus) mapped in our study influences several important parameters of TB infection: mycobacteria proliferation in the lungs, severity of lung pathology, and regulation of early inflammatory response.

genetic control, tuberculosis, H2 complex, recombinant mouse strains, QTL mapping



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