Platelet-derived growth factor receptor alpha subunit deleted Patch mouse exhibits severe cardiovascular dysmorphogenesis

Patch (Ph) mice, whose platelet-derived growth factor receptor alpha subunit (alpha PDGFR) gene has been deleted, have been used to elucidate requirements for alpha PDGFR for normal murine development. In this report we evaluate the role of alpha PDGFR in cardiovascular development by using in situ hybridization to follow the changing pattern of alpha PDGFR expression in cardiovascular tissues after embryonic day 13, and comparing this pattern with the pattern of cardiovascular defects observed in homozygous Ph mutants. Both mesodermally derived and neural crest-derived components of the cardiovascular system are severely dysmorphic in Ph/Ph embryos and those structures most severely affected are those that normally express alpha PDGFR mRNA at the highest levels and for the longest duration. Ph/Ph vessels appear to be lined with a normal endothelium, but contain a reduced number of smooth muscle cells and are fragile during processing for histology. The myocardium is thin, the heart is small and dysmorphic, the valves are malformed, and the interventricular and interatrial septa of the heart are defective. In the outflow tract, the spectrum of defects includes both persistent truncus arteriosus and double outlet right ventricle. This pattern of abnormalities is consistent with the hypothesis that deletion of alpha PDGFR results in a functional ablation of cranial neural crest cells, and that mesodermally derived components of the vascular system also require alpha PDGFR.