Phenotypes associated with this allele

• Allele Symbol: Scn5a^tm2.1Care
• Allele Name: targeted mutation 2.1, Carol Ann Remme
• Allele ID: MGI:5705587
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn5a^tm2.1Care/Scn5a^tm2.1Care	B6J.129P2(Cg)-Scn5a^tm2.1Care	MGI:5751745

Genotype
MGI:5751745

hm1

• Allelic Composition: Scn5a^tm2.1Care/Scn5a^tm2.1Care
• Genetic Background: B6J.129P2(Cg)-Scn5a^tm2.1Care

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

mortality/aging

mortality/aging ( J:224433 )

N • unexpectedly, homozygotes are born at normal Mendelian ratios and are viable throughout adulthood in the absence of apparent illesses or increased mortality

cardiovascular system

cardiovascular system phenotype ( J:224433 )

N • at 3-5 months of age, homozygotes have normal heart weight:body weight ratios and show no signs of cardiac fibrosis, inflammatory infiltrates, or cardiomyocyte hypertrophy

N • heart rate and QTc interval are not significantly altered

abnormal impulse conducting system conduction ( J:224433 )

• optical mapping in isolated Langendorff-perfused hearts showed significantly increased total left ventricular activation times and significantly decreased longitudinal and transversal conduction velocities in mutant ventricles relative to wild-type ventricles

• ventricular conduction velocity is preferentially reduced in the transversal direction to myocardial fiber orientation, leading to increased anisotropy of ventricular conduction (increased longitudinal/transversal conduction velocity ratio)

abnormal atrioventricular bundle conduction ( J:224433 )

• atrial and atrioventricular and, most notably, His-ventricular conduction are significantly slower in mutant hearts relative to wild-type hearts

prolonged PR interval ( J:224433 )

• significant prolongation of the PR interval

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

prolonged P wave ( J:224433 )

• significant prolongation of the P wave

• increase in the flecainide-induced prolongation of the P wave compared to wild-type controls

prolonged QRS complex duration ( J:224433 )

• significant prolongation of the QRS duration

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

abnormal myocardial fiber physiology ( J:224433 )

• isolated ventricular cardiomyocytes show a ~36% reduction in peak sodium current (I_Na) density but no changes in voltage dependence of I_Na activation and inactivation

• surprisingly, peak I_Na density is drastically reduced by ~62% at the cardiomyocyte lateral membrane but remains normal at the intercalated disk region

• maximum action potential (AP) upstroke velocity (dV/dt_max) is reduced by ~35% but resting membrane potential is not significantly altered

• a small but significant decrease is seen in the AP amplitude but AP durations at 30, 50, and 90% repolarization are not significantly altered

• no differences in Ba²⁺-sensitive inward rectifier potassium currents or in calcium channels are observed