Possible New Asthma Gene Discovery

Anil G. Menon, Ph.D.
University of Cincinnati
P30ES06096

Background: Aquaporin 5 (AQP5) is a protein found in alveolar, bronchial, and tracheal cells in mice and humans. The function of this protein is largely unknown, although previous studies have shown that it appears to have fluid clearance and airspace water permeability functions in the lungs. Using transgenic knockout mice, this study elucidates a possible role of AQP5 in bronchorestriction.

Advance: AQP5 deficient mice were shown to be hyperresponsive to bronchorestriction when challenged with a standard lung reactivity test using cholinergic stimulation. Sensitivity of airway smooth muscle tissue to constriction by acetyl choline is a classic characterization of both asthma and chronic obstructive pulmonary disease. These diseases are often treated with anticholinergic therapies.

Implication: Several genetic studies have linked the trait of airway hyperresponsiveness in mice and asthma susceptibility to the same chromosomal regions where AQP5 is located. The combined evidence of AQP5 lung expression patterns, responsiveness to cholinergic challenge, and the co-localization of AQP5 gene with chromosomal regions associated with airway hyperresponsiveness implicate this gene as a candidate for susceptibilty to bronchial hyperreactivity and asthma.