Abnormalities in the development of the cardiovascular system are among the most common congenital human birth defects. The mouse has proven to be an excellent model to study aberrant cardiovascular development, with the range of phenotypes observed in the mouse rivaling those encountered in humans. In many cases it is clear that complex phenotypes arise because impaired function causes an array of secondary defects that mask the original defect. Better tools are needed to characterize mutations that primarily affect cardiovascular function at early time points so primary defects in function are not missed. Here we will develop tools for using Optical Coherence Tomography as a routine method for studying cardiovascular abnormalities in mouse embryos. This method has a higher spatial resolution than currently used Ultrasound methods. The goal of this study is to show that OCT can be used to obtain sensitive measurements of heart function and blood flow, rivaling those that we have obtained in very early embryos using high-speed confocal microscopy. Our long term goal is to develop turn-key OCT systems for the routine phenotyping of mutant mice produced by large-scale screens.
7. Project Narrative This proposal will develop novel technology and methods to study congenital birth defects in mouse models. Approximately 35,000 children are born each year with a congenital defect in the cardiovascular system and this is the number one cause of birth-defect related deaths. Although there has been much progress in defining genes that are required for normal cardiovascular development, we need new methods to understand how mutations in these genes cause specific alterations in cardiac and endothelial cell morphogenesis that result in birth defects.
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