ArticleProceedings of the National Academy of Sciences of the United States of America2003
Susceptibility to tuberculosis: a locus on mouse chromosome 19 (Trl-4) regulates Mycobacterium tuberculosis replication in the lungs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 72 citations in OpenAlex.
- Immunological roads diverged: mapping tuberculosis outcomes in mice.Trends in microbiology · 2025Review
- Model systems to studyFrontiers in cellular and infection microbiology · 2025Review
- Genome-wide screen identifies host loci that modulate Mycobacterium tuberculosis fitness in immunodivergent mice.G3 (Bethesda, Md.) · 2023Article
- Article
- Genome-wide screen identifies host loci that modulatebioRxiv : the preprint server for biology · 2023Article
- Complement: The Road Less Traveled.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Mouse Models forPathogens (Basel, Switzerland) · 2022Review
- Functionally Overlapping Variants Control Tuberculosis Susceptibility in Collaborative Cross Mice.mBio · 2019Article
- Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies.Seminars in immunopathology · 2016Review
- The QTL within the H2 Complex Involved in the Control of Tuberculosis Infection in Mice Is the Classical Class II H2-Ab1 Gene.PLoS genetics · 2015Article
- Gr-1dimCD11b+ immature myeloid-derived suppressor cells but not neutrophils are markers of lethal tuberculosis infection in mice.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Animal welfare in studies on murine tuberculosis: assessing progress over a 12-year period and the need for further improvement.PloS one · 2012Review
- Article
- Joint effects of host genetic background and mycobacterial pathogen on susceptibility to infection.Infection and immunity · 2011Article
- Incidence and spread of Mycobacterium tuberculosis-associated infection among Aba Federal prison inmates in Nigeria.Journal of health, population, and nutrition · 2010Article
- Identification of a novel cerebral malaria susceptibility locus (Berr5) on mouse chromosome 19.Genes and immunity · 2010Article
- In mice, tuberculosis progression is associated with intensive inflammatory response and the accumulation of Gr-1 cells in the lungs.PloS one · 2010Article
- Man and mouse TB: contradictions and solutions.Tuberculosis (Edinburgh, Scotland) · 2009Article
- Genetic and functional characterization of the mouse Trl3 locus in defense against tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Disseminated and rapidly fatal tuberculosis in mice bearing a defective allele at IFN regulatory factor 8.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The mouse DBA/2 (D2) strain is very susceptible to infection with virulent Mycobacterium tuberculosis, whereas C57BL/6 (B6) is much more resistant. Infection of D2 and B6 mice with M. tuberculosis H37Rv by the respiratory route is biphasic: during the first 3 weeks, there is rapid bacterial growth in the lung of both strains, whereas beyond this point replication stops in B6 but continues in D2, causing rapidly fatal pulmonary disease. To identify the genes regulating growth of M. tuberculosis in the lungs of these two strains, 98 informative (B6 x D2) F2 mice were infected by the respiratory route with M. tuberculosis H37Rv (2 x 102 colony-forming units), and the extent of bacterial replication in the lungs at 90 days was used as a quantitative measure of susceptibility in a whole-genome scan. Quantitative trait locus mapping identified a major locus on chromosome 19 (Tuberculosis resistance locus-4, Trl-4; logarithm of odds 5.6), which regulated pulmonary replication of M. tuberculosis and accounted for 25% of the phenotypic variance. B6 alleles at Trl-4 were inherited in an incompletely dominant fashion and associated with reduced bacterial replication. An additional effect of a locus (Trl-3), previously shown to affect survival to i.v. infection with M. tuberculosis, was also noted. F2 mice homozygous for B6 alleles at both Trl-3 and Trl-4 were as resistant as B6 parents, whereas mice homozygous for D2 alleles were as susceptible as D2 parents. These results suggest a strong genetic interaction between Trl-3 and Trl-4 in regulating pulmonary replication of M. tuberculosis.
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