Modelling congenital malformations in mice - why genetic background matters

In humans, fetal survival depends on proper patterning and morphogenesis of the embryo and its accompanying placenta. Abnormal morphogenesis in the embryo underlies developmental abnormalities such as DiGeorge syndrome and Mandibulofacial dysostosis with microcephaly (MFDM), and results in increased morbidity and mortality. We use the mouse model to study the genetic and cellular basis of morphogenesis during the embryonic period; furthermore, the availability of next generation sequencing has enabled the rapid identification of genes associated with developmental abnormalities. The goals of my research program are (1) to use forward genetics to identify the genes responsible for malformations in human and mouse during pregnancy; (2) to use reverse genetics in the mouse model to characterize the cellular pathways regulated by genes implicated in developmental syndromes.