Phenotypes associated with this allele

• Allele Symbol: Scn1a^tm1Wac
• Allele Name: targeted mutation 1, William A Catterall
• Allele ID: MGI:3665322
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn1a^tm1Wac/Scn1a^tm1Wac	B6.129-Scn1a^tm1Wac	MGI:3690092
hm2	Scn1a^tm1Wac/Scn1a^tm1Wac	involves: 129S1/Sv * 129X1/SvJ * FVB/NJ	MGI:3818176
ht3	Scn1a^tm1Wac/Scn1a^+	129-Scn1a^tm1Wac	MGI:3690094
ht4	Scn1a^tm1Wac/Scn1a^+	B6.129-Scn1a^tm1Wac	MGI:3690093
ht5	Scn1a^tm1Wac/Scn1a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3690095
ht6	Scn1a^tm1Wac/Scn1a^+	involves: 129S1/Sv * 129X1/SvJ * FVB/NJ	MGI:3818175
cx7	Scn1a^tm1Wac/Scn1a^tm1Wac Scn8a^med-jo/Scn8a^+	involves: 129 * C57BL/6J * DBA/2WyDi * FVB/NJ	MGI:3818177
cx8	Scn1a^tm1Wac/Scn1a^+ Scn8a^med-jo/Scn8a^+	involves: 129 * C57BL/6J * DBA/2WyDi * FVB/NJ	MGI:3818178
cx9	Scn1a^tm1Wac/Scn1a^tm1Wac Tg(Scn1a*)RH9Aesc/0	involves: 129S1/Sv * 129X1/SvJ * FVB/NJ	MGI:3851213
cx10	Scn1a^tm1Wac/Scn1a^+ Tg(Scn1a*)RH9Aesc/0	involves: 129S1/Sv * 129X1/SvJ * FVB/NJ	MGI:3851214

Genotype
MGI:3690092

hm1

• Allelic Composition: Scn1a^tm1Wac/Scn1a^tm1Wac
• Genetic Background: B6.129-Scn1a^tm1Wac

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

mortality/aging

postnatal lethality, complete penetrance ( J:113149 )

• homozygotes die by P15; treatment with diazepam decreases seizure frequency but does not extend survival past P15

behavior/neurological

abnormal postural reflex ( J:113149 )

• problems progress to complete loss of postural control

impaired righting response ( J:113149 )

• at P15, mice require longer to recover from supine to prone position than wild-type and display a pronounced lack of coordination

tremors ( J:113149 )

• beginning at P9, neurological abnormalities progress to include mild limb tremors

ataxia ( J:113149 )

• beginning at P9, mutants exhibit ataxia

abnormal posture ( J:113149 )

• beginning at P9, neurological abnormalities progress to include side-to-side swaying

akinesia ( J:113149 )

• by P15, mutants become inactive except for periodic seizure activity

seizures ( J:113149 )

• beginning at P9, mutants exhibit seizures which progress in severity

convulsive seizures ( J:113149 )

• at P15, mice exhibit bilateral forelimb convulsive seizures

clonic seizures ( J:113149 )

• at P15, mice display generalized clonic seizures

nervous system

seizures ( J:113149 )

• beginning at P9, mutants exhibit seizures which progress in severity

convulsive seizures ( J:113149 )

• at P15, mice exhibit bilateral forelimb convulsive seizures

clonic seizures ( J:113149 )

• at P15, mice display generalized clonic seizures

abnormal nervous system electrophysiology ( J:113149 )

• isolated hippocampal pyramidal neurons show a substantial decrease in sodium current levels

• current densities in homozygotes (pA = 41 pA/pF) are decreased compared to wild-type (pA = 149 pA/pF)

abnormal action potential ( J:113149 )

• amplitude of the action potential is reduced and width is increased in response to injection of depolarizing current compared to wild-type interneurons

• peak of action potential is greater and minimum voltage after the action potential is more negative in wild-type compared to mutant interneurons

Genotype
MGI:3818176

hm2

• Allelic Composition: Scn1a^tm1Wac/Scn1a^tm1Wac
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/NJ

mortality/aging

postnatal lethality, complete penetrance ( J:129998 )

• all mice die by P15

Genotype
MGI:3690094

ht3

• Allelic Composition: Scn1a^tm1Wac/Scn1a⁺
• Genetic Background: 129-Scn1a^tm1Wac

mortality/aging

premature death ( J:113149 )

• Background Sensitivity: spontaneous deaths are 4-fold less (10% in 15 weeks) than in heterozygotes on a hybrid (congenic B6.129) background and 8-fold less than on a C57BL/6 background

Genotype
MGI:3690093

ht4

• Allelic Composition: Scn1a^tm1Wac/Scn1a⁺
• Genetic Background: B6.129-Scn1a^tm1Wac

mortality/aging

premature death ( J:113149 )

• Background Sensitivity: sporadic deaths are first seen in heterozygotes during weaning period, between P21 and P27; often, mice are found dead with hindlimbs outstretched and front paws tucked under the chin

• Background Sensitivity: many mice die during third postnatal week and 40% die by 15th week; this is more than on a coisogenic 129 background but less than on a mixed background

behavior/neurological

impaired contextual conditioning behavior ( J:188126 )

♂ • in the context-dependent fear-conditioning test, mice show reduced freezing behavior when returned to the shock cage 30 min and 24 hours later, indicating loss of fear-associated freezing behavior

impaired spatial learning ( J:188126 )

♂ • in the Barnes circular maze test, mice fail to improve their learning performance during 4 days of training

abnormal long-term spatial reference memory ( J:188126 )

♂ • in the Barnes circular maze test, mice have reduced spatial memory during probe trails at day 5

abnormal olfactory behavior ( J:188126 )

♂ • in a social odor test, mice show no preference for bedding from mouse cages as seen in wild-type mice, however mice exhibit normal olfaction in a food scent test

abnormal response to novel odor ( J:188126 )

♂ • in a Y-maze olfactory choice test, mice strongly avoid banana and male urine while wild-type mice have a strong preference for both

abnormal habituation to a novel odor ( J:188126 )

♂ • mice fail to show habituation/dishabituation to banana or male urine, but show normal response to food

♂ • however, mice have increased digging behavior when banana and male urine are presented, indicating detection of odors

increased anxiety-related response ( J:188126 )

♂ • mice enter open arms less frequently than wild-type mice and spend less time in the open arms of the elevated plus maze

♂ • mice exhibit increased immobility behavior when encountering a caged stranger mouse; this immobilization decreases distance traveled and increases immobilization time by 400%

increased thigmotaxis ( J:188126 )

♂ • adults spend less time in the center of the open field

increased grooming behavior ( J:188126 )

♂ • adults spend more time self-grooming

head bobbing ( J:113149 )

increased locomotor activity ( J:188126 )

♂ • adults travel father than wild-type mice during a 10 minute open-field test

circling ( J:188126 )

♂ • mice show increased circling behavior

abnormal nest building behavior ( J:188126 )

♂ • mice exhibit decreased nest-building activity

abnormal social investigation ( J:188126 )

♂ • mice interact less with a caged stranger mouse in an open field than wild-type mice

♂ • in reciprocal social interactions, mice show decreased duration of both non-aggressive and aggressive interactions

♂ • mice exhibit increased immobility behavior when encountering a caged stranger mouse; this immobilization decreases distance traveled and increases immobilization time by 400%

♂ • in a close-interaction analysis, mice avoid interacting with male social cues

abnormal response to social novelty ( J:188126 )

♂ • mice show no preference for the stranger mouse in a three-chamber test and show no discrimination between a new and a familiar mouse when a second stranger mouse is added, event though mice show preference for new objects

♂ • mice show no preference for the caged mouse when both an inanimate object and a caged stranger mouse are introduced simultaneously compared to wild-type mice that show a preference for the mouse

seizures ( J:113149 )

• heterozygotes first display recurring seizures between P21 and P21

nervous system

seizures ( J:113149 )

• heterozygotes first display recurring seizures between P21 and P21

abnormal nervous system electrophysiology ( J:113149 )

• during periods of continuous EEG recording, occurrence of spontaneous electrographic seizures can be observed as well as epileptiform interictal activity

• seizures begin with stereotypic behaviors such as Staub tail, myoclonic jerks and hindlimb flexions, progress to forelimb clonus and head bobbing and finish with relaxed muscle tone and an isoelectric period

• isolated hippocampal pyramidal neurons show a substantial decrease in sodium current levels

• current densities in heterozygotes (pA = 70 pA/pF) are decreased compared to wild-type (pA = 149 pA/pF)

abnormal action potential ( J:113149 )

• amplitude of the action potential is reduced and width is increased in response to injection of depolarizing current compared to wild-type interneurons

• peak of action potential is greater and minimum voltage after the action potential is more negative in wild-type compared to mutant interneurons

abnormal brain wave pattern ( J:113149 )

• during periods of continuous EEG recording, occurrence of spontaneous electrographic seizures can be observed as well as epileptiform interictal activity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:188126
Dravet syndrome		DOID:0080422	OMIM:607208	J:113149 , J:188126

Genotype
MGI:3690095

ht5

• Allelic Composition: Scn1a^tm1Wac/Scn1a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:113149 )

• Background Sensitivity: ~80% of heterozygotes die by 13 weeks of age on this background, a much higher incidence than on a congenic background (40%) or a coisogenic background (10%)

reproductive system

reduced fertility ( J:113149 )

Genotype
MGI:3818175

ht6

• Allelic Composition: Scn1a^tm1Wac/Scn1a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/NJ

mortality/aging

premature death ( J:129998 )

• 40% of mice die by P50 and 100% of mice by P125

nervous system

increased susceptibility to pharmacologically induced seizures ( J:129998 )

• following exposure to flurothyl, 63% of mice exhibit generalized tonic-clonic seizure with reduced latency compared to 9% of similarly treated wild-type mice

tonic-clonic seizures ( J:129998 )

• mice exhibit spontaneous tonic-clonic seizures

abnormal spike wave discharge ( J:129998 )

• mice exhibit ictal polyspike activity accompanied by stereotypic behavior unlike wild-type mice

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:129998 )

• following exposure to flurothyl, 63% of mice exhibit generalized tonic-clonic seizure with reduced latency compared to 9% of similarly treated wild-type mice

tonic-clonic seizures ( J:129998 )

• mice exhibit spontaneous tonic-clonic seizures

abnormal spike wave discharge ( J:129998 )

• mice exhibit ictal polyspike activity accompanied by stereotypic behavior unlike wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Dravet syndrome		DOID:0080422	OMIM:607208	J:129998

Genotype
MGI:3818177

cx7

• Allelic Composition: Scn1a^tm1Wac/Scn1a^tm1Wac; Scn8a^med-jo/Scn8a⁺
• Genetic Background: involves: 129 * C57BL/6J * DBA/2WyDi * FVB/NJ

mortality/aging

postnatal lethality, complete penetrance ( J:129998 )

• some mice survive beyond P15 but die by P18

Genotype
MGI:3818178

cx8

• Allelic Composition: Scn1a^tm1Wac/Scn1a⁺; Scn8a^med-jo/Scn8a⁺
• Genetic Background: involves: 129 * C57BL/6J * DBA/2WyDi * FVB/NJ

mortality/aging

mortality/aging ( J:129998 )

N • mice exhibit no abnormal lethality through P150

nervous system

nervous system phenotype ( J:129998 )

N • mice exhibit a normal threshold to flurothyl-induced generalized tonic-clonic seizure

abnormal spike wave discharge ( J:129998 )

• unlike Scn1a^tm1Wac heterozygotes, mice exhibit brief spike wave discharges associated with behavioral arrest that are not accompanied by behavioral components

behavior/neurological

abnormal spike wave discharge ( J:129998 )

• unlike Scn1a^tm1Wac heterozygotes, mice exhibit brief spike wave discharges associated with behavioral arrest that are not accompanied by behavioral components

Genotype
MGI:3851213

cx9

• Allelic Composition: Scn1a^tm1Wac/Scn1a^tm1Wac; Tg(Scn1a*)RH9Aesc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/NJ

mortality/aging

premature death ( J:150454 )

• a few mice survive beyond weaning but mice rarely survive past 6 months of age

postnatal lethality ( J:150454 )

• unlike homozygous mice not carrying the transgene which all die by P15, most mice carrying the transgene die between P17 and P21

Genotype
MGI:3851214

cx10

• Allelic Composition: Scn1a^tm1Wac/Scn1a⁺; Tg(Scn1a*)RH9Aesc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/NJ

mortality/aging

premature death ( J:150454 )

• substantial improvement in life span compared to heterozygous mice not carrying the transgene; 50% survival at 6 months of age compared to 25%