Heterozygous VMAT2 knockout mice display prolonged QT intervals: possible contributions to sudden death

Heterozygous knockout (KO) mice with half of wild-type levels of expression of the vesicular monoamine transporter (VMAT2) can suddenly die in midlife. To seek mechanisms for this sudden death, we have examined electrocardiogram (ECG) data telemetered from freely-moving heterozygote and wild-type littermate mice. Many ECG parameters were indistinguishable in mice of these two strains. However, heterozygous mice displayed prolonged QT intervals. These findings provide likely contributions to differences in vulnerability to lethal arrhythmias in these animals, and a candidate gene for contributions to human interindividual differences in vulnerability to cardiac arrhythmias.