Using Mouse Genetics to Understand Infectious Disease Pathogenesis
- Howard Hughes Medical Institute/Harvard Medical School, Department of Genetics, Boston, Massachusetts 02115, USA
This extract was created in the absence of an abstract.
The study of mouse and human genetic variation in infectious disease susceptibility (for review, see Malo and Skamene 1994; Hill 1998) should help to improve our knowledge of disease mechanisms by facilitating the identification of critical host proteins that modulate the infection process. Focusing on differences in disease susceptibility in humans will contribute to making progress in this field, but it is also possible to use mouse genetics to identify genes whose human orthologs are likely to affect the outcome of infections in man. It is impossible to adequately review all of the work that has been done to study the genetics of infectious disease susceptibility and pathogenesis. Therefore, I will discuss studies of two different bacterial infections. Although this is not a comprehensive approach, the examples help to illustrate my view that progress in understanding host susceptibility to infection will be facilitated by genetic studies of mouse models of infectious disease.
Susceptibility to Mycobacterial Infections
There are wide variations in susceptibility to mycobacterial disease in human and mouse populations (Bellamy 1998). Several mutations with profound effects on human mycobacterial susceptibility have been identified through the study of rare patients who presented with diseases caused by weakly pathogenic Mycobacterium spp. (Altare et al. 1998; Jouanguy et al. 1999a,b). In addition, it is likely that future genomewide screens in humans will solidify identification of novel genes involved in susceptibility to mycobacteria (Bellamy et al. 2000). However, mouse genetics offers a valuable complementary approach.
The study of mycobacterial pathogenesis and host defense has been powerfully influenced by the positional cloning of a mouse gene that affects susceptibility to diverse intracellular pathogens, including several (but not all) Mycobacterium spp., as well asSalmonella typhimurium and visceral Leishmaniasis pathogens (Vidal et al. 1993, 1995; North et al. 1999; Gruenheid and Gros …
