Phenotypes associated with this allele

• Allele Symbol: Scn1a^tm1.1Aesc
• Allele Name: targeted mutation 1.1, Andrew Escayg
• Allele ID: MGI:4458373
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn1a^tm1.1Aesc/Scn1a^tm1.1Aesc	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J	MGI:4950071
hm2	Scn1a^tm1.1Aesc/Scn1a^tm1.1Aesc	involves: 129X1/SvJ * C57BL/6J * SJL	MGI:4458389
ht3	Scn1a^tm1.1Aesc/Scn1a^+	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J	MGI:4950070
ht4	Scn1a^tm1.1Aesc/Scn1a^+	involves: 129X1/SvJ * C57BL/6J * SJL	MGI:4458390
cx5	Kcnq2^Nmf134/Kcnq2^+ Scn1a^tm1.1Aesc/Scn1a^+	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J	MGI:4950073
cx6	Scn1a^tm1.1Aesc/Scn1a^tm1.1Aesc Scn8a^med-jo/Scn8a^+	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * DBA/2WyDi	MGI:4950075
cx7	Scn1a^tm1.1Aesc/Scn1a^+ Scn8a^med-jo/Scn8a^+	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * DBA/2WyDi	MGI:4950074
cx8	Scn1a^tm1.1Aesc/Scn1a^+ Tg(Eno2-Scn2a1*)Q54Mm/0	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * SJL/J	MGI:4950072

Genotype
MGI:4950071

hm1

• Allelic Composition: Scn1a^tm1.1Aesc/Scn1a^tm1.1Aesc
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J

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

mortality/aging

postnatal lethality, complete penetrance ( J:170734 )

• 50% mortality by P10.5 and 100% lethality by P25

Genotype
MGI:4458389

hm2

• Allelic Composition: Scn1a^tm1.1Aesc/Scn1a^tm1.1Aesc
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:161191 )

• average life span is 18.5 days with mice dying between P16 and P26

nervous system

nervous system phenotype ( J:161191 )

N • mice exhibit normal neuronal cell abundance and cell viability

seizures ( J:161191 )

• mice exhibit visible seizures at P16 unlike wild-type mice

• seizures last 30 to 90 seconds and consist of excessive jumping, repetitive jerking of all four limbs, head nodding, and clonus of the forelimbs and tail unlike wild-type mice

maximal tonic hindlimb extension seizures ( J:161191 )

• observed in some seizures

environmentally induced seizures ( J:161191 )

• mice exhibit decreased threshold and latency to onset of tonic febrile seizure compared with similarly treated wild-type mice

clonic seizures ( J:161191 )

tonic seizures ( J:161191 )

• mice exhibit decreased threshold and latency to onset of tonic febrile seizure compared with similarly treated wild-type mice

impaired ability to fire action potentials ( J:161191 )

• Gaba-ergic interneurons exhibit decreased action potential firing compared with wild-type mice

abnormal GABA-mediated receptor currents ( J:161191 )

• mice exhibit a trend towards increased current density in GABA-ergic pyramidal neurons and a decrease in total sodium current amplitude in bipolar neurons compared with wild-type cells

• after repeated depolarization, GABA-ergic neurons exhibit a greater decrease in current than in wild-type neurons and slower recovery from inactivation

growth/size/body

decreased body weight ( J:161191 )

• at P18

weight loss ( J:161191 )

• at P15

behavior/neurological

seizures ( J:161191 )

• mice exhibit visible seizures at P16 unlike wild-type mice

• seizures last 30 to 90 seconds and consist of excessive jumping, repetitive jerking of all four limbs, head nodding, and clonus of the forelimbs and tail unlike wild-type mice

maximal tonic hindlimb extension seizures ( J:161191 )

• observed in some seizures

environmentally induced seizures ( J:161191 )

• mice exhibit decreased threshold and latency to onset of tonic febrile seizure compared with similarly treated wild-type mice

clonic seizures ( J:161191 )

tonic seizures ( J:161191 )

• mice exhibit decreased threshold and latency to onset of tonic febrile seizure compared with similarly treated wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
generalized epilepsy with febrile seizures plus		DOID:0060170		J:161191

Genotype
MGI:4950070

ht3

• Allelic Composition: Scn1a^tm1.1Aesc/Scn1a⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:170734 )

• average latency to flurothyl-induced generalized tonic-clonic seizures is 21% shorter than in wild-type mice, indicating reduced thresholds to induced seizures

nervous system

increased susceptibility to pharmacologically induced seizures ( J:170734 )

• average latency to flurothyl-induced generalized tonic-clonic seizures is 21% shorter than in wild-type mice, indicating reduced thresholds to induced seizures

Genotype
MGI:4458390

ht4

• Allelic Composition: Scn1a^tm1.1Aesc/Scn1a⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * SJL

Spontaneous seizure in an Scn1a^tm1.1Aesc/Scn1a⁺ mouse

nervous system

seizures ( J:161191 )

• mice exhibit low levels of spontaneous generalized seizures characterized by stereotypic motor behaviors unlike wild-type mice

increased susceptibility to pharmacologically induced seizures ( J:161191 )

• latency to generalized tonic clonic seizures induced by flurothyl is reduced compared to in similarly treated wild-type mice

• however, treatment with valporic acid (VPA) restores latency to normal and susceptibility to kainic acid-induced seizures is normal

environmentally induced seizures ( J:161191 )

• mice exhibit decreased threshold and latency to onset of tonic febrile seizure compared with similarly treated wild-type mice

tonic seizures ( J:161191 )

• mice exhibit decreased threshold and latency to onset of tonic febrile seizure compared with similarly treated wild-type mice

tonic-clonic seizures ( J:161191 )

• latency to generalized tonic clonic seizures induced by flurothyl is reduced compared to in similarly treated wild-type mice

• however, treatment with valporic acid (VPA) restores latency to normal

abnormal spike wave discharge ( J:161191 )

• seizures are associated with spike discharges at least two times the amplitude of background unlike in wild-type mice

abnormal GABA-mediated receptor currents ( J:161191 )

• mice exhibit a trend towards increased current density in GABA-ergic pyramidal neurons and a decrease in total sodium current amplitude in bipolar neurons compared with wild-type cells

• after repeated depolarization, GABA-ergic neurons exhibit a greater decrease in current than in wild-type neurons and slower recovery from inactivation

behavior/neurological

seizures ( J:161191 )

• mice exhibit low levels of spontaneous generalized seizures characterized by stereotypic motor behaviors unlike wild-type mice

increased susceptibility to pharmacologically induced seizures ( J:161191 )

• latency to generalized tonic clonic seizures induced by flurothyl is reduced compared to in similarly treated wild-type mice

• however, treatment with valporic acid (VPA) restores latency to normal and susceptibility to kainic acid-induced seizures is normal

environmentally induced seizures ( J:161191 )

• mice exhibit decreased threshold and latency to onset of tonic febrile seizure compared with similarly treated wild-type mice

tonic seizures ( J:161191 )

• mice exhibit decreased threshold and latency to onset of tonic febrile seizure compared with similarly treated wild-type mice

tonic-clonic seizures ( J:161191 )

• latency to generalized tonic clonic seizures induced by flurothyl is reduced compared to in similarly treated wild-type mice

• however, treatment with valporic acid (VPA) restores latency to normal

abnormal spike wave discharge ( J:161191 )

• seizures are associated with spike discharges at least two times the amplitude of background unlike in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
generalized epilepsy with febrile seizures plus		DOID:0060170		J:161191

Genotype
MGI:4950073

cx5

• Allelic Composition: Kcnq2^Nmf134/Kcnq2⁺; Scn1a^tm1.1Aesc/Scn1a⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J

behavior/neurological

convulsive seizures ( J:170734 )

• mutants begin to display spontaneous generalized seizures starting at P16, most being myoclonic jerks, a few generalized tonic-clonic seizures, and one mouse showing partial motor seizure

• generalized seizures are periodically followed by tonic extension of the hindlimbs

tonic-clonic seizures ( J:170734 )

• mutants show a few generalized tonic-clonic seizures

mortality/aging

decreased survivor rate ( J:170734 )

• 47% of mutants survive for more than 100 days

postnatal lethality, incomplete penetrance ( J:170734 )

• sporadic death begins to occur at P19, with 42% mortality by P25

nervous system

convulsive seizures ( J:170734 )

• mutants begin to display spontaneous generalized seizures starting at P16, most being myoclonic jerks, a few generalized tonic-clonic seizures, and one mouse showing partial motor seizure

• generalized seizures are periodically followed by tonic extension of the hindlimbs

tonic-clonic seizures ( J:170734 )

• mutants show a few generalized tonic-clonic seizures

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
generalized epilepsy with febrile seizures plus		DOID:0060170		J:170734

Genotype
MGI:4950075

cx6

• Allelic Composition: Scn1a^tm1.1Aesc/Scn1a^tm1.1Aesc; Scn8a^med-jo/Scn8a⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * DBA/2WyDi

mortality/aging

decreased survivor rate ( J:170734 )

• 47% of mutants survive for over 100 days

postnatal lethality, incomplete penetrance ( J:170734 )

• 25% mortality at P25

Genotype
MGI:4950074

cx7

• Allelic Composition: Scn1a^tm1.1Aesc/Scn1a⁺; Scn8a^med-jo/Scn8a⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * DBA/2WyDi

behavior/neurological

behavior/neurological phenotype ( J:170734 )

N • average latency to flurothyl-induced generalized tonic-clonic seizures is 50% longer when compared to single heterozygous Scn1a mice, but no different from wild-type indicating that seizure thresholds are restored to normal levels

Genotype
MGI:4950072

cx8

• Allelic Composition: Scn1a^tm1.1Aesc/Scn1a⁺; Tg(Eno2-Scn2a1*)Q54Mm/0
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * SJL/J

behavior/neurological

convulsive seizures ( J:170734 )

• mutants begin to exhibit spontaneous partial motor seizures and generalized tonic-clonic seizures at P16

• general seizures last 45-100 seconds, during which time mice experience repetitive jerking of all four limbs and neck, running, and jumping, and tail clonus; seizures often end with tonic hindlimb extension, indicative of a severe seizure

tonic-clonic seizures ( J:170734 )

• mutants begin to exhibit generalized tonic-clonic seizures at P16

mortality/aging

postnatal lethality, complete penetrance ( J:170734 )

• sporadic death begins to occur at P16, with 100% mortality by P24

nervous system

convulsive seizures ( J:170734 )

• mutants begin to exhibit spontaneous partial motor seizures and generalized tonic-clonic seizures at P16

• general seizures last 45-100 seconds, during which time mice experience repetitive jerking of all four limbs and neck, running, and jumping, and tail clonus; seizures often end with tonic hindlimb extension, indicative of a severe seizure

tonic-clonic seizures ( J:170734 )

• mutants begin to exhibit generalized tonic-clonic seizures at P16

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
generalized epilepsy with febrile seizures plus		DOID:0060170		J:170734