Phenotypes associated with this allele

• Allele Symbol: Atp1a3⁺
• Allele Name: wild type
• Allele ID: MGI:2430038
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Atp1a3^tm1.1Kwk/Atp1a3^+	B6JJcl.Cg-Atp1a3^tm1.1Kwk/Kwk	MGI:5572813
ht2	Atp1a3^tm1.1Tmklh/Atp1a3^+	B6JRj.129S1-Atp1a3^tm1.1Tmklh	MGI:6163608
ht3	Atp1a3^Myk/Atp1a3^+	B6NCr.129S1-Atp1a3^Myk	MGI:4356170
ht4	Atp1a3^tm1b(EUCOMM)Hmgu/Atp1a3^+	C57BL/6N-Atp1a3^tm1b(EUCOMM)Hmgu/H	MGI:5756743
ht5	Atp1a3^tm1Ling/Atp1a3^+	involves: 129 * Black Swiss	MGI:3697485
ht6	Atp1a3^tm1Ute/Atp1a3^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6162678
ht7	Atp1a3^tm1Mika/Atp1a3^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6197063
ht8	Atp1a3^Myk/Atp1a3^+	involves: 129S1/SvImJ * C57BL/6J * C57BL/6NCr	MGI:4356174
ht9	Atp1a3^Myk/Atp1a3^+	involves: 129S1/SvImJ * C57BL/6J * C57BL/6NCr * FVB/NCr	MGI:4356173
cx10	Atp1a3^Myk/Atp1a3^+ Tg(Atp1a3)1Stcl/0	B6NCr.Cg-Atp1a3^Myk Tg(Atp1a3)1Stcl	MGI:6163488
cx11	Atp1a3^Myk/Atp1a3^+ Tg(Atp1a3)1Stcl/0	involves: 129S1/SvImJ * C57BL/6 * SJL	MGI:4356323

Genotype
MGI:5572813

ht1

• Allelic Composition: Atp1a3^tm1.1Kwk/Atp1a3⁺
• Genetic Background: B6JJcl.Cg-Atp1a3^tm1.1Kwk/Kwk

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

nervous system

nervous system phenotype ( J:210870 )

N • mice exhibit normal paired-pulse ratio and excitatory synaptic transmissions

abnormal CNS synaptic transmission ( J:210870 )

• response to electrical stimulation suggests decreased threshold of molecular layer interneurons

increased miniature inhibitory postsynaptic current frequency ( J:210870 )

• higher frequency compared to in wild-type Purkinje cells

• however, amplitude distribution and mean amplitude are normal

behavior/neurological

dystonia ( J:210870 )

• dystonic response to kainite injection is sustained longer with later recovery and larger D4/D5 response (number of events) than in wild-type mice

• however, the mean duration of individual events is normal

enhanced coordination ( J:210870 )

• on a rotarod and a balance beam

hyperactivity ( J:210870 )

• in home cage and open field

homeostasis/metabolism

abnormal xenobiotic pharmacokinetics ( J:210870 )

• dystonic response to kainite injection is sustained longer with later recovery and larger D4/D5 response (number of events) than in wild-type mice

• however, the mean duration of individual events is normal

muscle

dystonia ( J:210870 )

• dystonic response to kainite injection is sustained longer with later recovery and larger D4/D5 response (number of events) than in wild-type mice

• however, the mean duration of individual events is normal

Genotype
MGI:6163608

ht2

• Allelic Composition: Atp1a3^tm1.1Tmklh/Atp1a3⁺
• Genetic Background: B6JRj.129S1-Atp1a3^tm1.1Tmklh

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:254463 )

• induced by pentylenetetrazole

preweaning lethality, incomplete penetrance ( J:254463 )

• fewer than expected mice are present at 3 weeks of age

behavior/neurological

behavior/neurological phenotype ( J:254463 )

N • mice do not exhibit spontaneous seizures

abnormal behavior ( J:254463 )

• in an elevated plus maze, mice do not discriminate between open and closed arms and spend more time in the open arms compared with wild-type mice

increased susceptibility to pharmacologically induced seizures ( J:254463 )

• induced by pentylenetetrazole with increased lethality

impaired passive avoidance behavior ( J:254463 )

• mice exhibit reduced latency to re-enter the dark compartment compared with wild-type mice

• however, clonazepam-treatment normalizes performance

abnormal habituation to a new environment ( J:254463 )

• minimal habituation in an open field

• in response to handling

impaired spatial learning ( J:254463 )

• in the Barnes Maze, mice do not exhibit increased latency to enter the escape tube but walk past the tube multiple times before entering compared with wild-type mice

hyperactivity ( J:254463 )

• in an open field test

nervous system

nervous system phenotype ( J:254463 )

N • CA1 pyramidal neurons exhibit normal excitability

increased susceptibility to pharmacologically induced seizures ( J:254463 )

• induced by pentylenetetrazole with increased lethality

abnormal dentate gyrus morphology ( J:254463 )

• large number of pyknotic nuclei within the dentate gyrus granule cell layer

abnormal hippocampus granule cell morphology ( J:254463 )

• reduced hippocampal dentate gyrus granule cells

abnormal action potential ( J:254463 )

• reduced rate of decay and slower initial discharge rate

• however, mice exhibit normal threshold of induction and steady-state electroresponsive behavior

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:254463 )

• induced by pentylenetetrazole

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
alternating hemiplegia of childhood		DOID:0050635	OMIM:104290 OMIM:614820 OMIM:PS104290	J:254463

Genotype
MGI:4356170

ht3

• Allelic Composition: Atp1a3^Myk/Atp1a3⁺
• Genetic Background: B6NCr.129S1-Atp1a3^Myk

mortality/aging

premature death ( J:151948 )

• maximal tonic hindlimb extension is followed by death

behavior/neurological

abnormal behavior ( J:180250 , J:262367 )

• in the Porsolt forced swim test, mice spend a longer time active than wild-type mice, indicating increased motivation (J:180250)

• chronic lithium carbonate and valproic acid treatment reduces the behavioral abnormalities of mutants (J:180250)

• treatment with SL327, an inhibitor of ERK, and rostafuroxin, a compound that selectively displaces ouabain from the Na⁺,K⁺-ATPase reduces the behavioral abnormalities of mutants (J:180250)

• mice take longer to find a hidden platform and swim further compared with wild-type mice (J:262367)

• however, swim speed and floating is normal (J:262367)

abnormal sensitization to xenobiotic ( J:180250 )

• mice show increased sensitivity to low dose of D-amphetamine, showing increased ambulation, rearing, stereotypy, and circling behavior compared to wild-type mice

enhanced conditioned place preference behavior ( J:180250 )

• mice show a greater preference for reward compared to wild-type mice, consuming more sucrose solution relative to water, and initially consuming more sucrose solution before the choice test

impaired contextual conditioning behavior ( J:262367 )

abnormal habituation ( J:180250 )

• mice do not habituate hole-board exploration

• the amount of rearing increases over time in mutants but decreases over time in wild-type mice, suggesting impaired habituation

decreased anxiety-related response ( J:180250 )

• mice have greater locomotor activity in the center compared with wild-type mice, suggesting decreased anxiety-like behavior

• in the elevated plus maze, mice make more open-arm entries and exploratory head dips and show a preference for the open arms

• in the light-dark box, mice spend a higher percentage of time in the light and do not show a preference for the dark compartment

increased thigmotaxis ( J:262367 )

• in a Morris water maze due to reduced behavioral flexibility

abnormal response to novel object ( J:180250 )

• mice explore objects and nosepoke more frequently than wild-type mice in the novel-object test and hole-board test

abnormal startle reflex ( J:180250 )

• deficit in startle habituation

impaired coordination ( J:262367 )

• after training, mice on a balance beam exhibit more hind foot slips and take more time to cross than wild-type mice

abnormal gait ( J:180250 )

• walking path of mice is chaotic

increased locomotor activity ( J:180250 )

• in the novel open field, mice show hyperambulation, faster walking speed, and decreased freezing than wild-type mice

• mice are more hyperactive in the dark but not in response to light

prolonged circadian behavior period ( J:180250 )

• mice entrain to light and shown normal circadian periods in a 12 hour light:12 hour dark environment, however, when external zeitgebers are removed, mice show an extended endogenous circadian period of 25 hours because of an increase in activity compared to 23.5 hours in wild-type mice

abnormal sleep pattern ( J:180250 )

• mice have more wake time than wild-type mice across 24 hours

abnormal non-rapid eye movement sleep pattern ( J:180250 )

• REM sleep latency, as measured by the average duration of non-REM sleep that precedes entrance into REM sleep, is reduced

abnormal paradoxical sleep pattern ( J:180250 )

• in the light phase, mice show shorter non-REM sleep bout length

decreased frequency of paradoxical sleep ( J:180250 )

• in the light phase, mice show reduced number of REM sleep bouts

abnormal seizure response to inducing agent ( J:180250 )

• Background Sensitivity: while mutants backcrossed to C57BL/6NCr mice for 12 generations show increased susceptibility to stress-induced seizures, mutants backcrossed for 20 generations do not exhibit stress-induced seizure activity

environmentally induced seizures ( J:151948 )

• 3 of 9 mice exhibit immediate induced convulsive seizure upon shaking of their cage

• however, treatment with valproic acid reduces cage-shaking-induced seizures and transfection with the wild-type copy of the gene prevents cage-shaking-induced seizures

convulsive seizures ( J:151948 )

• at 4 weeks of age, mice exhibit spontaneous, recurrent behavioral convulsive seizures unlike wild-type mice

• seizures can be evoked by vestibular stress

• seizures begin with running and leaping, behavioral arrest, and Straub tail, are followed by whole body clonic jerking and falling, are accompanied by salivation, and occasionally progressed to maximal tonic hindlimb extension followed by death

• 3 of 9 mice exhibit immediate induced convulsive seizure upon shaking of their cage

abnormal spike wave discharge ( J:151948 )

• during behavioral seizures mice exhibit spike-waves characteristic of epileptic discharge

• vestibular stress induces intermittent sharp waves that increase in amplitude until generalized bilateral synchronous tonic-clonic seizure activity is observed

• superfusion with magnesium ion free artificial cerebrospinal fluid induces repeated synchronized ictal bursts in the CA3 and entorhinal cortex of more than 50% of slices unlike in similarly treated wild-type slices

• after theta burst stimulation, mice exhibit enhanced excitation-spike coupling compared to wild-type mice

nervous system

nervous system phenotype ( J:151948 )

N • mice exhibit normal synaptic transmission and synaptic plasticity

abnormal seizure response to inducing agent ( J:180250 )

• Background Sensitivity: while mutants backcrossed to C57BL/6NCr mice for 12 generations show increased susceptibility to stress-induced seizures, mutants backcrossed for 20 generations do not exhibit stress-induced seizure activity

environmentally induced seizures ( J:151948 )

• 3 of 9 mice exhibit immediate induced convulsive seizure upon shaking of their cage

• however, treatment with valproic acid reduces cage-shaking-induced seizures and transfection with the wild-type copy of the gene prevents cage-shaking-induced seizures

convulsive seizures ( J:151948 )

• at 4 weeks of age, mice exhibit spontaneous, recurrent behavioral convulsive seizures unlike wild-type mice

• seizures can be evoked by vestibular stress

• seizures begin with running and leaping, behavioral arrest, and Straub tail, are followed by whole body clonic jerking and falling, are accompanied by salivation, and occasionally progressed to maximal tonic hindlimb extension followed by death

• 3 of 9 mice exhibit immediate induced convulsive seizure upon shaking of their cage

abnormal spike wave discharge ( J:151948 )

• during behavioral seizures mice exhibit spike-waves characteristic of epileptic discharge

• vestibular stress induces intermittent sharp waves that increase in amplitude until generalized bilateral synchronous tonic-clonic seizure activity is observed

• superfusion with magnesium ion free artificial cerebrospinal fluid induces repeated synchronized ictal bursts in the CA3 and entorhinal cortex of more than 50% of slices unlike in similarly treated wild-type slices

• after theta burst stimulation, mice exhibit enhanced excitation-spike coupling compared to wild-type mice

increased brain enzyme/coenzyme activity ( J:180250 )

• increase in total brain Na⁺,K⁺-ATPase activity

abnormal temporal lobe morphology ( J:151948 )

• mice exhibit medial temporal sclerosis

abnormal hippocampus pyramidal cell morphology ( J:151948 )

• mice exhibit aberrant membranous whorls in the hippocampal pyramidal neurons unlike in wild-type mice

abnormal neuron physiology ( J:180250 )

• neurons exhibit higher resting intracellular free calcium and show prolonged glutamate-evoked intracellular free calcium transients

abnormal sensorimotor gating ( J:180250 )

decreased prepulse inhibition ( J:180250 )

• deficit in prepulse inhibition

growth/size/body

decreased body size ( J:151948 )

• at 9 weeks

decreased body weight ( J:151948 , J:262367 )

• at 9 weeks (J:151948)

• at 4 and 8 weeks in male and female mice (J:262367)

• Background Sensitivity: unlike mice maintained on a mix background, female mice on a C57BL/6NCr congenic background exhibit decreased body weight (J:262367)

homeostasis/metabolism

increased brain enzyme/coenzyme activity ( J:180250 )

• increase in total brain Na⁺,K⁺-ATPase activity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
alternating hemiplegia of childhood		DOID:0050635	OMIM:104290 OMIM:614820 OMIM:PS104290	J:262367
bipolar disorder		DOID:3312		J:180250 , J:208021

Genotype
MGI:5756743

ht4

• Allelic Composition: Atp1a3^{tm1b(EUCOMM)Hmgu}/Atp1a3⁺
• Genetic Background: C57BL/6N-Atp1a3^{tm1b(EUCOMM)Hmgu}/H
• Cell Lines: HEPD0831_2_H02

Data Sources

IMPC Data for Atp1a3

behavior/neurological

increased exploration in new environment ( J:211773 )

♀

IMPC - HAR

decreased anxiety-related response ( J:211773 )

♀

IMPC - HAR

abnormal locomotor behavior ( J:211773 )

IMPC - HAR

hyperactivity ( J:211773 )

♀

IMPC - HAR

homeostasis/metabolism

improved glucose tolerance ( J:211773 )

♂

IMPC - HAR

Genotype
MGI:3697485

ht5

• Allelic Composition: Atp1a3^tm1Ling/Atp1a3⁺
• Genetic Background: involves: 129 * Black Swiss

behavior/neurological

enhanced behavioral response to addictive substance ( J:117414 )

• increase in peak activity elicited by methamphetamine

abnormal spatial learning ( J:117414 )

• increased latency to find the platform in a Morris water maze

hyperactivity ( J:117414 )

• significant increase in activity in the first 4 time intervals in an open field

• increase in peak activity elicited by methamphetamine

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:117414 )

N • circulating levels of corticosterone, norepinephrine, dopamine, serotonin, and their metabolites are all similar to wild-type mice

Genotype
MGI:6162678

ht6

• Allelic Composition: Atp1a3^tm1Ute/Atp1a3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:262419 )

• one of three mice exhibiting spontaneous seizures exhibits premature death

• of three of four mice kindled mice

behavior/neurological

behavior/neurological phenotype ( J:262419 )

N • mice exhibit normal cued conditioning, grip strength and tail flick task response

abnormal behavior ( J:262419 )

• mice take longer to find a hidden platform or crawl onto a marked platform compared with wild-type mice

• mice exhibit normal grip strength

abnormal long-term object recognition memory ( J:262419 )

• mice exhibit equal preference for two identical objects in a novel object task

decreased anxiety-related response ( J:262419 )

• in an open field test, mice exhibit increased activity including in the center area compared with wild-type mice

limb grasping ( J:262419 )

dystonia ( J:262419 )

• in 15 of 16 mice, predominantly upon exposure to water

tremors ( J:262419 )

• during the beam-walking task

ataxia ( J:262419 )

• severe during the beam-walking task

impaired coordination ( J:262419 )

• mice take longer to cross a beam, exhibit more hindlimb slips, and often use their forelimbs to drag themselves across unlike wild-type mice

• however, mice exhibit normal performance on an accelerated rotarod

short stride length ( J:262419 )

hyperactivity ( J:262419 )

• in an open field test, mice exhibit increased activity including in the center area compared with wild-type mice

hemiplegia ( J:262419 )

• reversible hemiplegia or hemipareses in 14 of 35 mice at between 8 and 28 weeks of age often during handling

• hemiplegias become bilateral and alternated within the same spell

hemiparesis ( J:262419 )

• reversible hemiplegia or hemipareses in 14 of 35 mice at between 8 and 28 weeks of age often during handling

increased thermal nociceptive threshold ( J:262419 )

• longer latency to response

seizures ( J:262419 )

• spontaneous and recurrent

increased susceptibility to pharmacologically induced seizures ( J:262419 )

• reduced latency to seizure onset induced by flurothyl

increased kindling response ( J:262419 )

• longer after discharge duration after achieving the fully kindled state

nervous system

seizures ( J:262419 )

• spontaneous and recurrent

increased susceptibility to pharmacologically induced seizures ( J:262419 )

• reduced latency to seizure onset induced by flurothyl

increased kindling response ( J:262419 )

• longer after discharge duration after achieving the fully kindled state

abnormal CNS synaptic transmission ( J:262419 )

• increased excitability with polyspikes in 5 of 6 mice induced by 30 1 Hz pulses with gradual increase in number of spikes and area, increased area of polyspike in response to paired-pulse stimulation, and larger spreading depression duration and area

• however, the fEPSP slope and amplitude are normal during repetitive stimulation

growth/size/body

growth/size/body region phenotype ( J:262419 )

N • mice exhibit normal trunk length

decreased body weight ( J:262419 )

♂ • at 6, 8, 9 and 11 weeks in male mice

♂ • however, female mice exhibit normal weight

muscle

dystonia ( J:262419 )

• in 15 of 16 mice, predominantly upon exposure to water

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
alternating hemiplegia of childhood		DOID:0050635	OMIM:104290 OMIM:614820 OMIM:PS104290	J:262419

Genotype
MGI:6197063

ht7

• Allelic Composition: Atp1a3^tm1Mika/Atp1a3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

premature death ( J:264408 )

• mice exhibit increased mortality, with highest mortality in the second quarter of life and no mice surviving beyond 264 days

• 33% of mice die during a witnessed seizure

growth/size/body

decreased body size ( J:264408 )

• mice are smaller at weaning

decreased body weight ( J:264408 )

♀ • weights of females, but not males, are decreased at P100

behavior/neurological

abnormal long-term object recognition memory ( J:264408 )

• in the novel object recognition (episodic memory) test, mice do not show preference for the novel object when one of the familiar objects is replaced with the novel object as seen in controls

decreased exploration in new environment ( J:264408 )

• mice spend less time in the peripheral zone and more time exploring the central squares of the open field, indicating decreased exploratory behavior

abnormal response to novel object ( J:264408 )

• mice exhibit decreased discrimination between novel and familiar objects

abnormal motor capabilities/coordination/movement ( J:264408 )

• in the open-field, mice engage in brief spells of limb-dragging, indicating motor performance abnormalities

limb grasping ( J:264408 )

• mice exhibit more hind-limb clasping during tail suspension

dystonia ( J:264408 )

• mice exhibit paroxysmal spells of hemiplegia and dystonia in response to exposure to water and to stress in the forced swim test, with 63% of mice experiencing dystonia after water submersion

impaired coordination ( J:264408 )

• mice fall earlier and at lower speeds on the accelerating rotarod

• mice require more time to transverse both the large and small beams, having difficulty gripping the beam with their hind-limbs and having a greater number of hind-limb slips

• 7 of 8 mice fall while trying to transverse the small beam

• however, grip strength is normal

abnormal gait ( J:264408 )

• mice exhibit a wider hind-limb stance but normal front-limb stance

short stride length ( J:264408 )

decreased locomotor activity ( J:264408 )

• mice exhibit reduced spontaneous locomotor behavior

• mice show initially little movement when placed in the open-field, with latency to begin locomotion lasting up to 40 seconds in some cases

hemiplegia ( J:264408 )

• mice exhibit episodes of hemiplegia or seizures around time of weaning at P21-P28, either spontaneously or upon stimulation like introduction to new cage

• 75% of mice experience hemiplegia after water submersion

• vestibular stimulation results in a longer episode of immobility than in controls and produces hemiplegia in all mice

• 3 month old mice treated with flunarizine exhibit shorter duration of hemiplegic episodes induced by the forced swim test, however the number of hemiplegic spells does not change and neither a long term beneficial or detrimental effect on behavioral tests is seen

seizures ( J:264408 )

• mice have spontaneous seizures in the first few days of life and exhibit episodes of hemiplegia or seizures around time of weaning at P21-P28 either spontaneously or upon stimulation like introduction to new cage

• mice exhibit spontaneous recurrent behavioral seizures, with multiple recurrences of the seizures, 2-4 per day, reaching Racine Class IV or V with forelimb clonus, rearing, and rapid, repetitive jerking movements

• hippocampal electrographic seizure activity is recorded during behavioral seizures

abnormal seizure response to inducing agent ( J:264408 )

• vestibular stimulation results in a longer episode of immobility than in controls and produces Racine stage IV seizures in 3/4 of mice

increased kindling response ( J:264408 )

• EEG recordings at the kindled state show that mice require fewer number of stimulations to elicit the first class IV/V seizures and to reach the fully kindled state, more class IV/V events per stimulation, and longer After-Discharge Duration of the class IV/V seizures at the fully kindled state

muscle

dystonia ( J:264408 )

• mice exhibit paroxysmal spells of hemiplegia and dystonia in response to exposure to water and to stress in the forced swim test, with 63% of mice experiencing dystonia after water submersion

nervous system

seizures ( J:264408 )

• mice have spontaneous seizures in the first few days of life and exhibit episodes of hemiplegia or seizures around time of weaning at P21-P28 either spontaneously or upon stimulation like introduction to new cage

• mice exhibit spontaneous recurrent behavioral seizures, with multiple recurrences of the seizures, 2-4 per day, reaching Racine Class IV or V with forelimb clonus, rearing, and rapid, repetitive jerking movements

• hippocampal electrographic seizure activity is recorded during behavioral seizures

abnormal seizure response to inducing agent ( J:264408 )

• vestibular stimulation results in a longer episode of immobility than in controls and produces Racine stage IV seizures in 3/4 of mice

increased kindling response ( J:264408 )

• EEG recordings at the kindled state show that mice require fewer number of stimulations to elicit the first class IV/V seizures and to reach the fully kindled state, more class IV/V events per stimulation, and longer After-Discharge Duration of the class IV/V seizures at the fully kindled state

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
alternating hemiplegia of childhood		DOID:0050635	OMIM:104290 OMIM:614820 OMIM:PS104290	J:264408

Genotype
MGI:4356174

ht8

• Allelic Composition: Atp1a3^Myk/Atp1a3⁺
• Genetic Background: involves: 129S1/SvImJ * C57BL/6J * C57BL/6NCr

mortality/aging

premature death ( J:151948 )

• maximal tonic hindlimb extension is followed by death

nervous system

nervous system phenotype ( J:151948 )

N • mice exhibit normal synaptic transmission and synaptic plasticity

environmentally induced seizures ( J:151948 )

• seizures can be evoked by vestibular stress

• mice exhibit spike wave discharge after cage shaking

• however, treatment with valproic acid reduces cage-shaking-induced seizures and transfection with the wild-type copy of the gene prevents cage-shaking-induced seizures

convulsive seizures ( J:151948 )

• at 4 weeks of age, mice exhibit spontaneous, recurrent behavioral convulsive seizures unlike wild-type mice

• seizures can be evoked by vestibular stress

• seizures begin with running and leaping, behavioral arrest, and Straub tail, are followed by whole body clonic jerking and falling, are accompanied by salivation, and occasionally progressed to maximal tonic hindlimb extension followed by death

• at 16 weeks, mice exhibit spontaneous seizures

abnormal spike wave discharge ( J:151948 )

• during behavioral seizures, mice exhibit spike-waves characteristic of epileptic discharge

• vestibular stress induces intermittent sharp waves that increase in amplitude until generalized bilateral synchronous tonic-clonic seizure activity is observed

• superfusion with magnesium ion free artificial cerebrospinal fluid induces repeated synchronized ictal bursts in the CA3 and entorhinal cortex of more than 50% of slices unlike in similarly treated wild-type slices

• after theta burst stimulation, mice exhibit enhanced excitation-spike coupling compared to wild-type mice

• mice exhibit numerous electrographic seizures unlike wild-type mice

• mice exhibit spike wave discharge after cage shaking

abnormal temporal lobe morphology ( J:151948 )

• mice exhibit medial temporal sclerosis

abnormal hippocampus pyramidal cell morphology ( J:151948 )

• mice exhibit aberrant membranous whorls in the hippocampal pyramidal neurons unlike in wild-type mice

growth/size/body

decreased body size ( J:151948 )

• at 9 weeks

decreased body weight ( J:151948 )

• at 9 weeks

behavior/neurological

environmentally induced seizures ( J:151948 )

• seizures can be evoked by vestibular stress

• mice exhibit spike wave discharge after cage shaking

• however, treatment with valproic acid reduces cage-shaking-induced seizures and transfection with the wild-type copy of the gene prevents cage-shaking-induced seizures

convulsive seizures ( J:151948 )

• at 4 weeks of age, mice exhibit spontaneous, recurrent behavioral convulsive seizures unlike wild-type mice

• seizures can be evoked by vestibular stress

• seizures begin with running and leaping, behavioral arrest, and Straub tail, are followed by whole body clonic jerking and falling, are accompanied by salivation, and occasionally progressed to maximal tonic hindlimb extension followed by death

• at 16 weeks, mice exhibit spontaneous seizures

abnormal spike wave discharge ( J:151948 )

• during behavioral seizures, mice exhibit spike-waves characteristic of epileptic discharge

• vestibular stress induces intermittent sharp waves that increase in amplitude until generalized bilateral synchronous tonic-clonic seizure activity is observed

• superfusion with magnesium ion free artificial cerebrospinal fluid induces repeated synchronized ictal bursts in the CA3 and entorhinal cortex of more than 50% of slices unlike in similarly treated wild-type slices

• after theta burst stimulation, mice exhibit enhanced excitation-spike coupling compared to wild-type mice

• mice exhibit numerous electrographic seizures unlike wild-type mice

• mice exhibit spike wave discharge after cage shaking

Genotype
MGI:4356173

ht9

• Allelic Composition: Atp1a3^Myk/Atp1a3⁺
• Genetic Background: involves: 129S1/SvImJ * C57BL/6J * C57BL/6NCr * FVB/NCr

nervous system

astrocytosis ( J:151948 )

• Background Sensitivity: mice exhibit astrogliosis unlike on a background lacking FVB/N

microgliosis ( J:151948 )

• Background Sensitivity: mice exhibit microglial activation unlike on a background lacking FVB/N

immune system

microgliosis ( J:151948 )

• Background Sensitivity: mice exhibit microglial activation unlike on a background lacking FVB/N

hematopoietic system

microgliosis ( J:151948 )

• Background Sensitivity: mice exhibit microglial activation unlike on a background lacking FVB/N

cellular

astrocytosis ( J:151948 )

• Background Sensitivity: mice exhibit astrogliosis unlike on a background lacking FVB/N

microgliosis ( J:151948 )

• Background Sensitivity: mice exhibit microglial activation unlike on a background lacking FVB/N

Genotype
MGI:6163488

cx10

• Allelic Composition: Atp1a3^Myk/Atp1a3⁺; Tg(Atp1a3)1Stcl/0
• Genetic Background: B6NCr.Cg-Atp1a3^Myk Tg(Atp1a3)1Stcl

behavior/neurological

behavior/neurological phenotype ( J:262367 )

N • unlike Atp1a3^Myk heterozygotes, mice exhibit normal coordination and contextual fear conditioning

abnormal behavior ( J:262367 )

• mice take longer to find a hidden platform and swim further compared with wild-type mice

• however, swim speed and floating is normal

increased thigmotaxis ( J:262367 )

• in a Morris water maze due to reduced behavioral flexibility

growth/size/body

growth/size/body region phenotype ( J:262367 )

N • unlike Atp1a3^Myk heterozygotes, mice exhibit normal body weight

Genotype
MGI:4356323

cx11

• Allelic Composition: Atp1a3^Myk/Atp1a3⁺; Tg(Atp1a3)1Stcl/0
• Genetic Background: involves: 129S1/SvImJ * C57BL/6 * SJL

nervous system

nervous system phenotype ( J:151948 )

N • cage shaking does not induce seizures as it does for Atp1a3^Myk heterozygotes

behavior/neurological

behavior/neurological phenotype ( J:180250 )

N • mice perform at normal levels in the open field, elevated plus maze and light-dark box