Phenotypes Associated with This Genotype

Genotype
MGI:5699868

• Allelic Composition: Scn1a^tm1.1Swl/Scn1a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6JNarl

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

mortality/aging

premature death ( J:221045 )

• Background Sensitivity: 46.2% of mice die by postnatal week 4 on a mixed 129 and C57BL/6JNarl background compared to only 5.4% on a 129 background

• mice that have severe seizure attacks die at the average age of P21.9

behavior/neurological

environmentally induced seizures ( J:221045 )

• the threshold temperatures for hyperthermia-induced seizures are lower than in wild-type mice at postnatal week 3-5 and postnatal week 16-20, indicating increased susceptibility to hyperthermia-induced seizures

tonic-clonic seizures ( J:221045 )

• spontaneous epileptiform activity begins as early as P20, with mice showing generalized tonic-clonic seizures

• 44.8% of mice exhibit spontaneous seizures at P20 to P25

• average seizure duration is about 45.8 seconds and the mean latency from first seizure to death is 13.9 hours

nervous system

environmentally induced seizures ( J:221045 )

• the threshold temperatures for hyperthermia-induced seizures are lower than in wild-type mice at postnatal week 3-5 and postnatal week 16-20, indicating increased susceptibility to hyperthermia-induced seizures

tonic-clonic seizures ( J:221045 )

• spontaneous epileptiform activity begins as early as P20, with mice showing generalized tonic-clonic seizures

• 44.8% of mice exhibit spontaneous seizures at P20 to P25

• average seizure duration is about 45.8 seconds and the mean latency from first seizure to death is 13.9 hours

abnormal hippocampus granule cell morphology ( J:221045 )

• dentate gyrus granule cells exhibit abnormal dendritic arborization at postnatal week 4, with a reduction in the number of dendritic segments and the total dendritic length

abnormal dendrite morphology ( J:221045 )

• dentate gyrus granule cells exhibit abnormal dendritic arborization at postnatal week 4, with a reduction in the number of dendritic segments and the total dendritic length

abnormal dendritic spine morphology ( J:221045 )

• dendritic spines in dentate gyrus neurons do not undergo normal pruning during postnatal week 3 to week 4, leaving spine density unchanged

abnormal synaptic transmission ( J:221045 )

• mice exhibit elevation in basal excitatory transmission in dente gyrate

abnormal miniature excitatory postsynaptic currents ( J:221045 )

• in dentate gyrus granule cells, the frequency of spontaneous EPSC is increased

• however, sEPSC amplitude is normal

• mEPSCs show a higher frequency in dentate gyrus granule cells in the presence of the sodium channel blocker TTX, however mEPSC amplitude is similar to controls

abnormal miniature inhibitory postsynaptic currents ( J:221045 )

• in dentate gyrus granule cells, the frequency of sIPSCs is reduced

• however, sIPSC amplitude is normal

decreased paired-pulse ratio ( J:221045 )

• synaptic response of brief paired stimuli with 50 ms intervals indicates a lower paired-pulse ratio than in controls suggesting elevated release probability of excitatory terminals in granule cells