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Genetic control of susceptibility to bacterial infections in mouse models
Steven Lam-Yuk-Tseung1, Philippe Gros
1Department of Biochemistry, Cancer Center, McGill University, Montreal, Canada. philippe.gros@staff.mcgill.ca
Abstract:
Historically, the laboratory mouse (Mus musculus) has been the experimental model of choice to study pathophysiology of infection with bacterial pathogens, including natural and acquired host defence mechanisms. Inbred mouse strains differ significantly in their degree of susceptibility to infection with various human pathogens such as Mycobacterium, Salmonella, Legionella and many others. Segregation analyses and linkage studies have indicated that some of these differences are under simple genetic control whereas others behave as complex traits. Major advances in genome technologies have greatly facilitated positional cloning of single gene effects. Thus, a number of genes playing a key role in initial susceptibility, progression and outcome of infection have been uncovered and the functional characterization of the encoded proteins has provided new insight into the molecular basis of antimicrobial defences of polymorphonuclear leukocytes, macrophages, as well as T and B lymphocytes. The multigenic control of susceptibility to infection with certain human pathogens is beginning to be characterized by quantitative trait locus mapping in genome wide scans. This review summarizes recent progress on the mapping, cloning and characterization of genes and proteins that affect susceptibility to infection with major intracellular bacterial pathogens.
Insights
Laboratory mice are crucial for studying bacterial infections and host defenses. Genetic studies reveal single genes and complex traits influencing susceptibility to pathogens like Mycobacterium and Salmonella.
Area of Science:
- Immunology
- Genetics
- Microbiology
Background:
- The laboratory mouse (Mus musculus) is a primary model for studying bacterial infections and host defense mechanisms.
- Genetic variations in mouse strains significantly impact susceptibility to human pathogens (e.g., Mycobacterium, Salmonella, Legionella).
Purpose of the Study:
- To review recent advancements in identifying and characterizing genes and proteins that influence host susceptibility to intracellular bacterial pathogens.
Main Methods:
- Utilizing segregation analyses and linkage studies to identify genetic controls of infection susceptibility.
- Employing advanced genome technologies for positional cloning of single-gene effects.
- Applying quantitative trait locus (QTL) mapping for genome-wide scans of multigenic traits.
Main Results:
- Discovery of numerous genes critical for infection susceptibility, progression, and outcome.
- Functional characterization of encoded proteins offering insights into antimicrobial defenses (polymorphonuclear leukocytes, macrophages, T and B lymphocytes).
- Beginning characterization of multigenic control of pathogen susceptibility through QTL mapping.
Conclusions:
- Genetic factors, ranging from single genes to complex traits, play a vital role in host defense against bacterial pathogens.
- Advances in genomics have accelerated the identification and understanding of genes governing infection outcomes.
- Further research into these genetic determinants is essential for understanding host-pathogen interactions and developing novel therapeutic strategies.