Related Experiment Videos
Severity of tuberculosis in mice is linked to distal chromosome 3 and proximal chromosome 9
C Lavebratt1, A S Apt, B V Nikonenko
1Neurogenetics Unit, Center for Molecular Medicine, Karolinska Hospital, 171 76 Stockholm, Sweden. catharina.lavebratt@cmm.ki.se
Abstract:
Genetic factors play a role in host response to infection with Mycobacterium tuberculosis, the number one infectious killer worldwide. Mice of the inbred strains I/St and A/Sn show significant differences in disease severity after intravenous injection of a lethal dose of the virulent human isolate M. tuberculosis H37Rv. Following challenge with H37Rv, only I/St mice have rapid body weight loss and short survival times. A genome wide analysis for linkage with body weight after M. tuberculosis H37Rv infection was done in (A/SnxI/St)F1xI/St mice. Among females, quantitative trait loci (QTLs) on chromosomes 9 and 3 were significantly linked to postinfection body weight (logarithm of the odds ratio [LOD] scores of 6.68 and 3.92, respectively). Suggestive linkages were found for QTLs on chromosomes 8 and 17 (LOD scores of 3.01 and 2.95, respectively). For males, QTLs on chromosomes 5 and 10 showed suggestive linkages (LOD scores of 3.03 and 2.31, respectively). These linkages can be used to identify candidate regions for tuberculosis susceptibility loci in the human genome.
Insights
Genetic factors influence tuberculosis (TB) severity. Researchers identified specific mouse chromosomes linked to body weight changes after Mycobacterium tuberculosis infection, offering insights into human TB susceptibility genes.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Host genetic factors significantly impact susceptibility and response to Mycobacterium tuberculosis (M. tuberculosis) infection.
- Significant differences in disease severity and survival are observed between mouse strains I/St and A/Sn following M. tuberculosis H37Rv challenge.
- I/St mice exhibit rapid body weight loss and reduced survival times post-infection.
Purpose of the Study:
- To identify genetic loci associated with host response to M. tuberculosis infection.
- To map quantitative trait loci (QTLs) influencing body weight changes after M. tuberculosis challenge in a mouse model.
Main Methods:
- Genome-wide linkage analysis was performed in a (A/SnxI/St)F1xI/St mouse cross.
- Body weight following M. tuberculosis H37Rv infection was measured and analyzed.
- Statistical analysis, including logarithm of the odds ratio (LOD) scores, was used to identify significant linkages.
Main Results:
- In female mice, significant QTLs linked to post-infection body weight were identified on chromosomes 9 (LOD=6.68) and 3 (LOD=3.92).
- Suggestive linkages in females were found on chromosomes 8 (LOD=3.01) and 17 (LOD=2.95).
- In male mice, suggestive linkages were observed on chromosomes 5 (LOD=3.03) and 10 (LOD=2.31).
Conclusions:
- The identified QTLs represent candidate regions for genetic loci influencing tuberculosis susceptibility.
- These findings provide a foundation for pinpointing specific genes involved in host response to M. tuberculosis.
- The study highlights the utility of mouse models in understanding the genetic basis of human infectious diseases.