Congenital heart valve defects have led to heart disease in thousands of people and yet, in most cases, their causes have been a mystery. Viruses, drugs, and other environmental factors have been blamed but little is known about which genes may go awry to cause valve defects. Nor is much known about how human heart valves develop normally. Ben Neel and colleagues have identified proteins that may play a role in heart valve development. The researchers found that mating those mutants with mice carrying a defective version of another gene, Shp2, produces even more striking abnormalities.
Most offspring die before birth.
Those that survive have massively overgrown aortic and pulmonic valves and develop heart disease as young adults. The findings appear in the March 1 Nature Genetics. So far, people suffering from congenital heart valve disease have not been found to carry mutant versions of the Egfr and Shp2 genes. In this regard, the mutant mice say more about how normal human valves arise than how they become defective. But Neel, HMS professor of medicine, believes the mice could shed light on what happens once defects develop.