Comparative analysis of mycobacterial infections in susceptible I/St and resistant A/Sn inbred mice

Comparative Analysis of T Lymphocytes Recovered from the Lungs of Mice Genetically Susceptible, Resistant, and Hyperresistant toMycobacterium tuberculosis-Triggered Disease

“…In particular, it was found that the severe course of the disease caused by i.v. M. tuberculosis H37Rv injection in mice of the I/St inbred strain contrasts sharply with its relatively mild development in mice of the A/Sn inbred strain (22,23). Genome-wide linkage analysis of the severity of TB showed a significant linkage with microsatellite loci on distal chromosome 3 and proximal chromosome 9 in females and suggestive linkages for both sexes with loci on chromosomes 5, 8, 10, and 17 (23).…”

A new coding mutation in the Tnf-α leader sequence in tuberculosis-sensitive I/St mice causes higher secretion levels of soluble TNF-α

“…3 It has been proposed that the amount of TNF-a at the site of infection determines if the cytokine is protective or destructive. 30 Ruuls et al 25 suggested a more prominent role for the soluble form in inflammation, but it has also been reported that the membrane form by itself is sufficient to mediate inflammation.…”

“…1 Compared to A/Sn mice, the I/St mice display a two times faster body weight loss, a 20-to 100-fold higher mycobacterial multiplication rate in spleens and lungs, and a more severe lung histopathology and less than half of the survival time. 2,3 These strains constitute a tool to study genetic factors controlling sensitivity to tuberculosis since they clearly differ in a number of parameters defining disease progression. Linkage analysis in crosses between I/St and A/Sn mice suggested a quantitative trait locus on chromosome 17, which implies an underlying gene that controls the variation in severity of disease among the offspring.…”

Efficacy of Isoniazid Therapy in Mice with Different Genetic Susceptibility to Infection

“…Among forty inbred mouse strains studied by our lab during last decades, mice of the I/St Strain demonstrated the highest of susceptibility to infection with M. tuberculosis strain H37Rv [1][2][3][4][5][6]. Unlike the majority of conventional mouse strains, after M. tuberculosis infection I/St mice form necrotic and hypoxic lung granulomas [6,7], similar to those in humans [8], and in another hyper-susceptible mouse strain C3HeB/FeJ [9].…”

“…Unlike the majority of conventional mouse strains, after M. tuberculosis infection I/St mice form necrotic and hypoxic lung granulomas [6,7], similar to those in humans [8], and in another hyper-susceptible mouse strain C3HeB/FeJ [9]. In numerous studies dissecting TB susceptibility genetic control by segregation analyses, most often mice of the C57BL/6 strain were used as a TB-resistant partner [10][11][12][13], although other strains appeared to be also helpful [2,3]. Taking into account dozens of studies in mice bearing knockout mutations in genes encoding key cytokines, chemokines and their receptors [14], one may conclude that mouse genetics of susceptibility to M. tuberculosis infection is relatively well characterized.…”