Genetic control of susceptibility to bacterial infections in mouse models.
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.
Lam-Yuk-Tseung
Steven
S
Department of Biochemistry, Cancer Center, McGill University, Montreal, Canada. philippe.gros@staff.mcgill.ca
Gros
Philippe
P
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D000818:Animals; D001424:Bacterial Infections / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D006801:Humans; D017136:Ion Transport; D008070:Lipopolysaccharides / Q000633:toxicity; D008562:Membrane Glycoproteins / Q000235:genetics; D008670:Metals / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009164:Mycobacterium Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D051193:Toll-Like Receptors; D000099173:Natural Resistance-associated Macrophage Protein 1
D000077329:Agammaglobulinaemia Tyrosine Kinase; D027682:Cation Transport Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008670:Metals; D011505:Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D000099173:Natural Resistance-associated Macrophage Protein 1