Phenotypes associated with this allele

• Allele Symbol: Scn1a^tm1.1Swl
• Allele Name: targeted mutation 1.1, Shu-Wha Lin
• Allele ID: MGI:5699848
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn1a^tm1.1Swl/Scn1a^tm1.1Swl	involves: 129S1/Sv * 129X1/SvJ * C57BL/6JNarl	MGI:5699870
ht2	Scn1a^tm1.1Swl/Scn1a^+	involves: 129S1/Sv * 129S2/SvPasCrl * 129X1/SvJ	MGI:5699851
ht3	Scn1a^tm1.1Swl/Scn1a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6JNarl	MGI:5699868

Genotype
MGI:5699870

hm1

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

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

mortality/aging

postnatal lethality, complete penetrance ( J:221045 )

• all mice die by P17

behavior/neurological

abnormal gait ( J:221045 )

• beginning at P9, pups exhibit an unstable gait that deteriorates progressively

tonic-clonic seizures ( J:221045 )

• as early as P12, pups develop spontaneous generalized tonic-clonic seizures that last from 1 to 3 min

growth/size/body

decreased body weight ( J:221045 )

• by P15, mice show lower body weight than wild-type mice

nervous system

tonic-clonic seizures ( J:221045 )

• as early as P12, pups develop spontaneous generalized tonic-clonic seizures that last from 1 to 3 min

Genotype
MGI:5699851

ht2

• Allelic Composition: Scn1a^tm1.1Swl/Scn1a⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPasCrl * 129X1/SvJ

mortality/aging

premature death ( J:221045 )

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

• however, most mice develop normally and are fertile

Genotype
MGI:5699868

ht3

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

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