This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sánchez, F.
Right arrow Articles by Lavebratt, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sánchez, F.
Right arrow Articles by Lavebratt, C.

 Previous Article  |  Next Article 

Infection and Immunity, January 2003, p. 126-131, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.126-131.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Multigenic Control of Disease Severity after Virulent Mycobacterium tuberculosis Infection in Mice

Fabio Sánchez,1 Tatiana V. Radaeva,2 Boris V. Nikonenko,2 Ann-Sophie Persson,1 Selim Sengul,1 Martin Schalling,1 Erwin Schurr,3 Alexander S. Apt,2 and Catharina Lavebratt1*

Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden,1 Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow 107564, Russia,2 McGill Center for the Study of Host Resistance, Montreal General Hospital, Montreal, H3G 1A4 Quebec, Canada3

Received 2 January 2002/ Returned for modification 12 February 2002/ Accepted 24 September 2002

Following challenge with virulent Mycobacterium tuberculosis, mice of the I/St inbred strain exhibit shorter survival time, more rapid body weight loss, higher mycobacterial loads in organs, and more severe lung histopathology than mice of the A/Sn strain. We previously performed a genome-wide scan for quantitative trait loci (QTLs) that control the severity of M. tuberculosis-triggered disease in [(A/Sn x I/St) F1 x I/St] backcross-1 (BC1) mice and described several QTLs that are significantly or suggestively linked to body weight loss. In the present study we expanded our analysis by including the survival time phenotype and by genotyping 406 (A/Sn x I/St) F2 mice for the previously identified chromosomal regions of interest. The previously identified 12-cM-wide QTL on distal mouse chromosome 3 was designated tbs1 (tuberculosis severity 1); the location of the QTL on proximal chromosome 9 was narrowed to a 9-cM interval, and this QTL was designated tbs2. Allelic variants of the tbs2 locus appeared to be involved in control of both body weight loss and survival time. Also, the data strongly suggested that a QTL located in the vicinity of the H-2 complex on chromosome 17 is involved in control of tuberculosis in mice of both genders, whereas the tbs1 locus seemed to have an effect on postinfection body weight loss in female mice. Interestingly, these loci appeared to interact with each other, which suggests that there might be a basic genetic network for the control of intracellular parasites. Overall, linkage data reported here for F2 mice are in agreement with, and add to, our previous findings concerning the control of M. tuberculosis-triggered disease in the BC1 segregation.

* Corresponding author. Mailing address: Center for Molecular Medicine, Karolinska Hospital L8:00, 171 76 Stockholm, Sweden. Phone: 46-8-5177 6524. Fax: 46-8-5177 3909. E-mail: catharina.lavebratt{at}cmm.ki.se.

Editor: S. H. E. Kaufmann

Infection and Immunity, January 2003, p. 126-131, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.126-131.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Huberle, A., Beyeen, A. D., Ockinger, J., Ayturan, M., Jagodic, M., de Graaf, K. L., Fissolo, N., Marta, M., Olofsson, P., Hultqvist, M., Holmdahl, R., Olsson, T., Weissert, R. (2009). Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barre Syndrome. J. Immunol. 182: 4432-4438 [Abstract] [Full Text]  
  • Marquis, J.-F., LaCourse, R., Ryan, L., North, R. J., Gros, P. (2009). Genetic and Functional Characterization of the Mouse Trl3 Locus in Defense against Tuberculosis. J. Immunol. 182: 3757-3767 [Abstract] [Full Text]  
  • Marquis, J.-F., LaCourse, R., Ryan, L., North, R. J., Gros, P. (2009). Disseminated and Rapidly Fatal Tuberculosis in Mice Bearing a Defective Allele at IFN Regulatory Factor 8. J. Immunol. 182: 3008-3015 [Abstract] [Full Text]  
  • Turner, J. K., McAllister, M. M., Xu, J. L., Tapping, R. I. (2008). The Resistance of BALB/cJ Mice to Yersinia pestis Maps to the Major Histocompatibility Complex of Chromosome 17. Infect. Immun. 76: 4092-4099 [Abstract] [Full Text]  
  • Marquis, J.-F., Nantel, A., LaCourse, R., Ryan, L., North, R. J., Gros, P. (2008). Fibrotic Response as a Distinguishing Feature of Resistance and Susceptibility to Pulmonary Infection with Mycobacterium tuberculosis in Mice. Infect. Immun. 76: 78-88 [Abstract] [Full Text]  
  • Yan, B.-S., Pichugin, A. V., Jobe, O., Helming, L., Eruslanov, E. B., Gutierrez-Pabello, J. A., Rojas, M., Shebzukhov, Y. V., Kobzik, L., Kramnik, I. (2007). Progression of Pulmonary Tuberculosis and Efficiency of Bacillus Calmette-Guerin Vaccination Are Genetically Controlled via a Common sst1-Mediated Mechanism of Innate Immunity. J. Immunol. 179: 6919-6932 [Abstract] [Full Text]  
  • Kondratieva, E. V., Evstifeev, V. V., Kondratieva, T. K., Petrovskaya, S. N., Pichugin, A. V., Rubakova, E. I., Averbakh, M. M. Jr., Apt, A. S. (2007). I/St Mice Hypersusceptible to Mycobacterium tuberculosis Are Resistant to M. avium. Infect. Immun. 75: 4762-4768 [Abstract] [Full Text]  
  • Pichugin, A. V., Petrovskaya, S. N., Apt, A. S. (2006). H2 complex controls CD4/CD8 ratio, recurrent responsiveness to repeated stimulations, and resistance to activation-induced apoptosis during T cell response to mycobacterial antigens. J. Leukoc. Biol. 79: 739-746 [Abstract] [Full Text]  
  • Smith, I., Nathan, C., Peavy, H. H. (2005). Progress and New Directions in Genetics of Tuberculosis: An NHLBI Working Group Report. Am. J. Respir. Crit. Care Med. 172: 1491-1496 [Abstract] [Full Text]  
  • Sakthianandeswaren, A., Elso, C. M., Simpson, K., Curtis, J. M., Kumar, B., Speed, T. P., Handman, E., Foote, S. J. (2005). The wound repair response controls outcome to cutaneous leishmaniasis. Proc. Natl. Acad. Sci. USA 102: 15551-15556 [Abstract] [Full Text]  
  • Majorov, K. B., Eruslanov, E. B., Rubakova, E. I., Kondratieva, T. K., Apt, A. S. (2005). Analysis of Cellular Phenotypes That Mediate Genetic Resistance to Tuberculosis Using a Radiation Bone Marrow Chimera Approach. Infect. Immun. 73: 6174-6178 [Abstract] [Full Text]  
  • Malik, S., Abel, L., Tooker, H., Poon, A., Simkin, L., Girard, M., Adams, G. J., Starke, J. R., Smith, K. C., Graviss, E. A., Musser, J. M., Schurr, E. (2005). Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease. Proc. Natl. Acad. Sci. USA 102: 12183-12188 [Abstract] [Full Text]  
  • Eruslanov, E. B., Lyadova, I. V., Kondratieva, T. K., Majorov, K. B., Scheglov, I. V., Orlova, M. O., Apt, A. S. (2005). Neutrophil Responses to Mycobacterium tuberculosis Infection in Genetically Susceptible and Resistant Mice. Infect. Immun. 73: 1744-1753 [Abstract] [Full Text]  
  • Nikonenko, B. V., Samala, R., Einck, L., Nacy, C. A. (2004). Rapid, Simple In Vivo Screen for New Drugs Active against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 48: 4550-4555 [Abstract] [Full Text]  
  • Kamath, A. B., Alt, J., Debbabi, H., Taylor, C., Behar, S. M. (2004). The Major Histocompatibility Complex Haplotype Affects T-Cell Recognition of Mycobacterial Antigens but Not Resistance to Mycobacterium tuberculosis in C3H Mice. Infect. Immun. 72: 6790-6798 [Abstract] [Full Text]  
  • Cardona, P.-J., Gordillo, S., Diaz, J., Tapia, G., Amat, I., Pallares, A., Vilaplana, C., Ariza, A., Ausina, V. (2003). Widespread Bronchogenic Dissemination Makes DBA/2 Mice More Susceptible than C57BL/6 Mice to Experimental Aerosol Infection with Mycobacterium tuberculosis. Infect. Immun. 71: 5845-5854 [Abstract] [Full Text]  
  • Mitsos, L.-M., Cardon, L. R., Ryan, L., LaCourse, R., North, R. J., Gros, P. (2003). Susceptibility to tuberculosis: A locus on mouse chromosome 19 (Trl-4) regulates Mycobacterium tuberculosis replication in the lungs. Proc. Natl. Acad. Sci. USA 100: 6610-6615 [Abstract] [Full Text]  
  • Majorov, K. B., Lyadova, I. V., Kondratieva, T. K., Eruslanov, E. B., Rubakova, E. I., Orlova, M. O., Mischenko, V. V., Apt, A. S. (2003). Different Innate Ability of I/St and A/Sn Mice To Combat Virulent Mycobacterium tuberculosis: Phenotypes Expressed in Lung and Extrapulmonary Macrophages. Infect. Immun. 71: 697-707 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»