ABSTRACT
Allergic asthma is a heterogeneous disease, which can be characterized by
high levels of allergen-specific immunoglobulin (Ig)E in serum, chronic
eosinophilic inflammation of the airway tissue and hyperreactivity of the
airways (AHR) to bronchospasmogenic stimuli. Genetic susceptibility to asthma appears to be due to multiple genes that interact with each other
and the environment. Although genetic linkage and association studies have
identified many susceptibility loci for specific asthma traits and identified a
number of susceptibility genes, fine-mapping and identification of all the
genes involved in asthma-related traits may prove to be extremely difficult
not in the least part due to epistatic interactions. Yet, in order to understand
the genetic basis of asthma, it is important to identify as many different sus-
ceptibility genes as possible and to determine their interactions. Although an animal model of asthma may not exhibit all aspects of human disease,
identification of genes involved in certain well-defined characteristics may
accelerate further human studies. Given the considerable homology between
the human and mouse genome, the mouse may prove to be a useful genetic
model organism for complex human diseases. Furthermore, genetic homogeneity and strictly controlled developmental (age) and environmental
(infection, food, and climate) conditions are major advantages of a mouse
model, as well as the fact that the mouse ‘‘toolbox’’ (gene-targeted mice
and genetic and physical map) is very well developed. The possibility to gene-
rate congenic lines makes it possible to determine if the phenotypic effect of
a locus is caused by one gene or by a combination of multiple closely linked
genes at the locus, something that cannot be done in humans.
