Phenotypes Associated with This Genotype

Genotype
MGI:3765987

• Allelic Composition: Scn5a^tm1Clhh/Scn5a⁺
• Genetic Background: involves: 129 * 129S/SvEv * C57BL/6J

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:127879 )

• following tail clipping one mouse exhibited generalized seizure and died

• however, the lifespan of other mice is normal

postnatal lethality, incomplete penetrance ( J:127879 )

• fewer than expected mice are recovered 3 to 4 weeks after birth

cardiovascular system

ventricular tachycardia ( J:127879 )

• unlike in wild-type mice, application of programmed electrical stimulation induced ventricular tachycardia in 8 of 9 mice

irregular heartbeat ( J:127879 )

• electrogram duration (EGD) during programmed electrical stimulation parallels (PES) arrhythmic tendencies

• unlike in wild-type mice, propranolol fails to suppress arrhythmias following treatment with isoproterenol

• isoproterenol does not affect arrhythmia status during PES whereas in wild-type mice it induces arrhythmic effects

• mexiletine suppresses arrhythmias in 4 of 5 mice without effecting EGD

abnormal impulse conducting system conduction ( J:127879 )

• hearts exhibit greater increases in electrogram duration (EGD) than wild-type hearts during programmed electrical stimulation (PES)

• EGD during PES parallels arrhythmic tendencies

• mice exhibit greater stimulus to response latencies measured at the beginning of the PES sequences than do wild-type mice

• mice exhibit larger ventricular effective refractory period than wild-type mice (37+/-7 msec compared to 29+/-6 msec)

• unlike in wild-type mice, 1 uM propranolol accentuates the increase in EGD as S1S2 intervals are shortened

• treatment with propranolol increases EGD

abnormal myocardial fiber physiology ( J:127879 )

• action potential is prolonged in myocytes (152+/-17.8 msec compared to 55+/-6.6 msec in wild-type cells)

• unlike in wild-type mice, myocytes exhibit early afterdepolarization and persistent sodium tail currents

behavior/neurological

seizures ( J:127879 )

• following tail clipping one mouse exhibited generalized seizure and died

nervous system

seizures ( J:127879 )

• following tail clipping one mouse exhibited generalized seizure and died

muscle

abnormal myocardial fiber physiology ( J:127879 )

• action potential is prolonged in myocytes (152+/-17.8 msec compared to 55+/-6.6 msec in wild-type cells)

• unlike in wild-type mice, myocytes exhibit early afterdepolarization and persistent sodium tail currents