"First, fruit flies were used to test for all possible pairwise genetic interactions between these genes that might disrupt the function of the simple fluid pumping fly heart," said Bier." These comprehensive genetic studies pointed to a particular pair of genes known as DSCAM and COL6A2 that resulted in the most severe defects when over-produced together."
Then the researchers tested the effects of increasing the levels of these genes in the hearts of experimental mice. They first generated genetic lines of mice having elevated activity of each of these genes in the heart and then genetically crossed these mice to create offspring that over-produced both genes together. The parental mice as well as their offspring were then tested for heart function and visible heart defects.
Mice having elevated levels of each gene separately were largely normal. But the offspring with extra levels of both genes suffered from severe cardiac defects. These heart defects were of two kinds. The first resembled one of the salient features of Down syndrome cardiac patients, in which blood shunts between the two atrial chambers of the heart through small holes in a septum that normally isolates these two chambers. The second defect, which is not frequently observed in Down syndrome patients, but is a common and very serious condition in the general population, was a thickening of the heart wallreferred to medically as cardiac hypertrophy.
"Such thickening of the heart wall greatly reduces heart function and can lead to fatal heart attacks, which indeed w
|Contact: Kim McDonald|
University of California - San Diego