Grant: Operating Grant

Asthma is a complex respiratory and immune disease. The environment and its interaction with the genetic make-up of the host determine the onset, progression and severity of the lung inflammatory response associated with asthma. The limited success in identifying genes regulating asthma is not only due to the inherent genetic complexity of the disease, but also to the very limited number of genetic models suitable for studying the disease. By taking advantage of a new mouse model of asthma together with a unique genetic platform, we have shown that genes confering susceptibility to asthma are tractable. We have identified several candidate mouse chromosomal regions that coincide with asthma susceptibility loci identified in humans, indicating that our approach will yield genes with a high probability of being relevant to the development of asthma. In this proposal our initial efforts will be directed towards identifying asthma susceptibility genes within a chromosomal region that has gone undetected in previous studies. This region shows a strong effect and therefore will be more easily amenable to gene identification. In addition, the region harbors several candidate genes that may provide new insights into the mechanisms of asthma susceptibility. Another important aspect of the proposal involves understanding the various pathological characteristics of asthma. It will address the question of whether the same genes and pathways underly asthma and allergy, and aid the identification of allergy susceptibility genes. We anticipate that the proposed studies will provide us with a better understanding of the molecular mechanisms underlying asthma which may enable the identification of new treatments and targets for new drugs.