Noninvasive Localization of Nuclear Factor of Activated T Cells c1−/− Mouse Embryos by Ultrasound Biomicroscopy-Doppler Allows Genotype-phenotype Correlation

Ultrasound biomicroscopy (UBM)-Doppler allows study of cardiovascular physiology in the in utero mouse embryo from embryonic day (E)8.25 onward. We determined the accuracy of localization of embryos by transabdominal, noninvasive 40-MHz UBM-Doppler imaging. Nuclear factor of activated T cells c1−/− mice lack semilunar valves, exhibit outflow tract regurgitation, and die in utero. In timed pregnant mice generated from heterozygote crosses, an UBM-derived map of the in situ litter was compared with a definitive laparotomy map, and UBM-Doppler cardiac screen attempted for each embryo. All 109 living and dead (nonresorbed) E10.5 to 17.5 embryos were imaged and accurately localized. All 10 embryos with reversed diastolic aortic flow and 7 of 9 dead embryos genotyped were nuclear factor of activated T cells c1−/−. In 30 embryos followed up serially over 1 to 2 days from E12.5 to E16.5, we again achieved 100% accuracy in localizing at follow-up. Noninvasive localization and UBM-Doppler analysis of in situ mouse embryos can provide accurate genotype-phenotype correlation, along with nontraumatic serial imaging of embryos.