Ultrahigh-Frequency Echocardiography of Autonomic Devoid Phox2B Homozygous Embryos Does Not Reveal a Significant Cardiac Phenotype before Embryo Death.

In vivo micro-imaging of mice is useful in studying the genetic basis of cardiac development in mutant embryos. We examined Phox2b mutant mice, which lack autonomic innervation to the heart and die in utero, and investigated whether this lack of innervation causes cardiac dysfunction during embryogenesis. A VisualSonics Vevo 2100 ultrahigh-frequency linear array ultrasound machine with 30- and 40-MHz probes was used to analyze embryo size, gross characteristics, ventricular contractility and rhythm. Phox2b mutant embryos underwent cessation of heartbeat and death at a greater rate than wild-type controls. We did not observe a hydrops phenotype or congenital heart defects in Phox2b mutants. Analysis of heart rhythm revealed no significant correlation with genotype. Absent these signs of a progressive pathology, we suggest that Phox2b mutant embryos likely die of sudden death secondary to acute arrhythmia. These data provide insight into the role of cardiac autonomic innervation during development.