We have used magnetic resonance microscopy to compare the cardiac anatomy of normal and NFATc knockout mice at an age of 13 days post conception. The embryos were injected with a contrast agent (Gd-DTPA conjugated to albumin), fixed in paraformaldehyde and then imaged at a field strength of 9.4 Tesla. The injection of contrast material allows us to make large (256x128x128), high resolution (60x40x40 microns voxel size) data sets in a reasonably short period of time (2 hours for four averages). We are then able to quantitatively assess the volumes of the fetal hearts. The NFATc knockout is embryonically lethal, with death occurring at 14.5 dpc, due to the failure of both pulmonary and aortic valves to develop. This should lead to regurgitation of the blood into the chambers, enlarging them. Preliminary results are that the left ventricle is actually smaller in the knockout relative to homozygote or heterozygote littermates. and analyzing the data sets using specialized software developed with the IDL programming language. We are proceeding to characterize other stages. Mice with genetic defects, specifically the knockouts of the NFATc, VCAM-1, and connexin43 genes, all of which have been shown to develop cardiac defects, will be studied in embryos at a variety of stages in order to delineate clearly the developmental process and understand the nature of the defects caused by the mutations. This knowledge will act as an important guide for future work in vivo.
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