Mouse Genome Informatics
phenotype observed in females
phenotype observed in males
N normal phenotype
• unlike human patients with a similar mutation, heterozygotes do not display sudden cardiac death

cardiovascular system
• significantly slower heart rate
• flecainide induced extreme sinus bradycardia and/or sinus arrest in 4 of 6 mice compared to 0 of 6 in wild-type controls
• epicardial mapping indicates slower conduction (increased activation time, reduced transverse conduction velocity) in the right ventricle but not in the left ventricle
• increase in the flecainide-induced prolongation of the PQ interval compared to wild-type controls
• significant prolongation of the PQ interval
• prolonged QRS duration
• increase in the flecainide-induced prolongation of the QRS interval compared to wild-type controls
• prolonged QTc interval
• more sinus pauses of longer duration
• however, no ventricular arrhythmias are detected
• prolonged action potential duration at frequencies less than 4 Hz and smaller dV/dt(max) at all frequencies tested
• ventricular myocytes show reduced peak sodium current densities and prolonged current decay half-life (at voltages from -45 to -25 mV) at room temperature
• upstroke velocity (dV/dt(max)) of the elicited action potential is reduced by 31% at -120 mV
• the current density of persistent sodium currents is significantly larger at voltages between -90 and -10 mV

Mouse Models of Human Disease
Brugada Syndrome 1; BRGDA1 601144 J:128657
Long QT Syndrome 3; LQT3 603830 J:128657