Phenotypes Associated with This Genotype

Genotype
MGI:3769904

• Allelic Composition: Scn5a^tm1Care/Scn5a⁺
• Genetic Background: FVB.129P2-Scn5a^tm1Care/Care

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

mortality/aging ( J:128657 )

N • unlike human patients with a similar mutation, heterozygotes do not display sudden cardiac death

cardiovascular system

decreased heart rate ( J:128657 )

• 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

abnormal impulse conducting system conduction ( J:128657 )

• epicardial mapping indicates slower conduction (increased activation time, reduced transverse conduction velocity) in the right ventricle but not in the left ventricle

prolonged PQ interval ( J:128657 )

• significant prolongation of the PQ interval

• increase in the flecainide-induced prolongation of the PQ interval compared to wild-type controls

prolonged QRS complex duration ( J:128657 )

• prolonged QRS duration

• increase in the flecainide-induced prolongation of the QRS interval compared to wild-type controls

prolonged QT interval ( J:128657 )

• prolonged QTc interval

abnormal sinoatrial node conduction ( J:128657 )

• more sinus pauses of longer duration

• however, no ventricular arrhythmias are detected

abnormal myocardial fiber physiology ( J:128657 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Brugada syndrome 1		DOID:0110218	OMIM:601144	J:128657
long QT syndrome 3		DOID:0110646	OMIM:603830	J:128657