Mouse Genome Informatics
ht
    Scn1atm1.1Kzy/Scn1a+
involves: 129P2/OlaHsd * C3HeB/FeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 21% of mice die suddenly by P150, with 38% of deaths occurring before P25 and 69% of deaths by P52

cardiovascular system
• 2-fold increase in both transient and persistent Na+ current density in isolated ventricular myocytes
• increase in activity of a tetrodotoxin-resistant Na+ current
• myocytes exhibit increased excitability, action potential duration prolongation, and increased incidence of triggered activity
• focal bradycardia
• injection of PTZ results in a sudden 32% decrease in the heart rate, which is further diminished with increasing doses of PTZ
• ECG recordings indicated idioventricular rhythm
• cardiac arrhythmias often precede spontaneous convulsive seizures and death
• precedes or occurs during convulsive seizures
• continuous radiotelemetric ECG recordings show QT prolongation, ventricular ectopic foci, idioventricular rhythms, beat-to-beat variability (R-R variability), ventricular fibrillation, focal bradycardia, and conduction abnormalities
• beat-to-beat (R-R) variability
• precedes or occurs during convulsive seizures
• myocytes exhibit increased excitability, action potential duration prolongation, and increased incidence of triggered activity

nervous system
• mice show increased susceptibility to PTZ induced convulsive seizures, showing bradycardia
• ECG recordings indicate that PTZ-induced seizures and death do not phenocopy the cardiac ECG phenotype of putative sudden unexpected death
• mice develop spontaneous seizures

behavior/neurological
• mice show increased susceptibility to PTZ induced convulsive seizures, showing bradycardia
• ECG recordings indicate that PTZ-induced seizures and death do not phenocopy the cardiac ECG phenotype of putative sudden unexpected death
• mice develop spontaneous seizures

Mouse Models of Human Disease
OMIM IDRef(s)
Epileptic Encephalopathy, Early Infantile, 6; EIEE6 607208 J:209093