Using an egg white protein called ovalbumin to induce an allergic reaction and inflammation in the lungs of mice, the researchers observed a dramatic elevation in the expression of SPDEF in the lung tissues of the affected animals. The animals also experienced hyper-production of thick mucous in their lungs. In mice where the SPDEF gene was switched off, inflammation and excessive mucous production did not occur, demonstrating the gene's potential as therapeutic or diagnostic target. Mice lacking SPDEF were unable to increase mucous production or develop goblet cells.

In mice where respiratory inflammation and excessive mucous production were present, the researchers report that SPDEF turned off genes involved in biological processes that help protect lung tissues from infection and damage. Conversely, SPDEF activated genes that promote inflammation and excessive mucous - in particular FOXA3, AGR2 and mucins.

By composition, mucous is a sugar-coated collection of large proteins that, in healthy conditions, help the body defend itself by collecting and then clearing out contaminants. In the case of AGR2 for example, the gene helps assemble mucous proteins by folding together different molecules. When SPDEF is over-expressed, it results in increased production of AGR2, which in turn promotes an over-abundance of protein folding and mucous production.

Dr. Whitsett cautioned it will be several years before the research results in a specific therapeutic approach that can be tested in people. In the meantime, his team has received several significant grants to conduct more extensive studies into the various genetic and molecular influences that control, or are controlled by, SPDEF and involved in excess mucous production.

Source: cincinnatichildrens