Preparing and organizing results from an ENU mutagenesis screen for congenital heart disease for public view

Abstract

Congenital heart disease (CHD) is one of the most common birth defects in humans. In addition, CHD is the leading cause of infant death. Ethylnitrosourea (ENU) is used to induce random single nucleotide polymorphisms in mice. Once the mice are have a mutation they are sent to the University of Pittsburgh for analysis to determine if the SNP is associated with cardiovascular defects. Each mutated mouse is used to breed its own mouse line. The ENU screen uses echocardiography, EFIC imaging, necropsy and exome sequencing to determine the phenotypes and genotypes of the mouse lines. The screen has identified novel genes in mice that may be potential causes of CHD in infants. The Bench to Bassinet program is a nationwide program that translates basic science to clinical trials. As part of this program, data gathered by the ENU screen in mice is organized and available to the public through Jackson Labs Mouse Genome Informatics Database. As of March 2013, 123 mouse lines covering many different types of cardiovascular and craniofacial defects have been made available to the public. Public health significance: Approximately 40,000 infants die from CHD each year. This research and this database enables collaboration among many researchers to identify the causal genes of CHD in infants, and hopefully an eventual means of prophylaxis