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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Scn1atm1.1Kzy
targeted mutation 1.1, Kazuhiro Yamakawa
MGI:5521534
Summary 3 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
ht1
Scn1atm1.1Kzy/Scn1a+ involves: 129P2/OlaHsd * C3HeB/FeJ MGI:6154327
ht2
Scn1atm1.1Kzy/Scn1a+ involves: 129P2/OlaHsd * C3HeB/FeJ * C57BL/6J MGI:5576947
ht3
Scn1atm1.1Kzy/Scn1a+ involves: 129P2/OlaHsd * C57BL/6 MGI:5521535


Genotype
MGI:6154327
ht1
Allelic
Composition
Scn1atm1.1Kzy/Scn1a+
Genetic
Background
involves: 129P2/OlaHsd * C3HeB/FeJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Scn1atm1.1Kzy mutation (2 available); any Scn1a mutation (114 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• death occurs in heat-induced seizures due to apnea, and bradycardia only occurs if there is apnea
• 38% of mice die spontaneously between P16 and P60 after a generalized seizure characterized by tonic hind limb extension

behavior/neurological
• mice develop spontaneous seizures
• nonfatal seizures are generalized with clonic limb contractions and include transient episodes of apnea and bradycardia that are less severe than during fatal seizures
• all spontaneous seizures with tonic hind limb extension are fatal
• maximal electroshock induces generalized seizures, but these seizures are less likely to cause apnea
• a rise in body temperature induces seizures in mutants, with first seizure occurring at an average of 39.67 degrees Celsius, leading to death in 18 of 21 mice after 3.53 seizures
• fatal heat-induced seizures are characterized by tonic hind limb extension or clonic limb contractions followed by a decrease in heart rate
• pre-treatment of mice with hypothermia-induced seizures with high-dose atropine prevents peri-ictal apnea and reduces the likelihood of tonic hind limb extension and death, but does not reduced the likelihood of seizures or the duration or severity of seizures
• pre-treatment of mice with hypothermia-induced seizures with N-methylscopalamine does not prevent apnea, bradycardia or death
• pre-treatment of mice with hypothermia-induced seizures with methylatrophine prevents bradycardia, death and apnea

cardiovascular system
• mice exhibit a rapid decrease in heart rate shortly after the onset of apnea during seizure but the heartbeat remains above 25-51% of control for 60 seconds after onset of apnea and continues for almost 4 minutes after the end of seizure, with slowly worsening bradycardia eventually leading to terminal asystole
• bradycardia during seizure never occurs without apnea or severely decreased breath amplitude
• mice anesthetized with isoflurane and switched from normoxia to anoxia exhibit bradycardia and show a decrease in QRS complex amplitude
• pretreatment of mice with atropine does not prevent the bradycardia induced by anoxia

nervous system
• mice develop spontaneous seizures
• nonfatal seizures are generalized with clonic limb contractions and include transient episodes of apnea and bradycardia that are less severe than during fatal seizures
• all spontaneous seizures with tonic hind limb extension are fatal
• maximal electroshock induces generalized seizures, but these seizures are less likely to cause apnea
• a rise in body temperature induces seizures in mutants, with first seizure occurring at an average of 39.67 degrees Celsius, leading to death in 18 of 21 mice after 3.53 seizures
• fatal heat-induced seizures are characterized by tonic hind limb extension or clonic limb contractions followed by a decrease in heart rate
• pre-treatment of mice with hypothermia-induced seizures with high-dose atropine prevents peri-ictal apnea and reduces the likelihood of tonic hind limb extension and death, but does not reduced the likelihood of seizures or the duration or severity of seizures
• pre-treatment of mice with hypothermia-induced seizures with N-methylscopalamine does not prevent apnea, bradycardia or death
• pre-treatment of mice with hypothermia-induced seizures with methylatrophine prevents bradycardia, death and apnea

respiratory system
• during seizure, mice develop central apnea; apnea occurs prior to bradycardia
• heat-induced seizures cause respiratory arrest and fatal heat-induced seizures always involve terminal apnea, with apnea occurring during the seizure or within seconds of the end of the seizure

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Dravet syndrome DOID:0080422 OMIM:607208
J:260796




Genotype
MGI:5576947
ht2
Allelic
Composition
Scn1atm1.1Kzy/Scn1a+
Genetic
Background
involves: 129P2/OlaHsd * C3HeB/FeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Scn1atm1.1Kzy mutation (2 available); any Scn1a mutation (114 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 21% of mice die suddenly by P150, with 38% of deaths occurring before P25 and 69% of deaths by P52

cardiovascular system
• 2-fold increase in both transient and persistent Na+ current density in isolated ventricular myocytes
• increase in activity of a tetrodotoxin-resistant Na+ current
• myocytes exhibit increased excitability, action potential duration prolongation, and increased incidence of triggered activity
• focal bradycardia
• injection of PTZ results in a sudden 32% decrease in the heart rate, which is further diminished with increasing doses of PTZ
• ECG recordings indicated idioventricular rhythm
• cardiac arrhythmias often precede spontaneous convulsive seizures and death
• precedes or occurs during convulsive seizures
• continuous radiotelemetric ECG recordings show QT prolongation, ventricular ectopic foci, idioventricular rhythms, beat-to-beat variability (R-R variability), ventricular fibrillation, focal bradycardia, and conduction abnormalities
• beat-to-beat (R-R) variability
• precedes or occurs during convulsive seizures
• myocytes exhibit increased excitability, action potential duration prolongation, and increased incidence of triggered activity

nervous system
• mice show increased susceptibility to PTZ induced convulsive seizures, showing bradycardia
• ECG recordings indicate that PTZ-induced seizures and death do not phenocopy the cardiac ECG phenotype of putative sudden unexpected death
• mice develop spontaneous seizures

behavior/neurological
• mice show increased susceptibility to PTZ induced convulsive seizures, showing bradycardia
• ECG recordings indicate that PTZ-induced seizures and death do not phenocopy the cardiac ECG phenotype of putative sudden unexpected death
• mice develop spontaneous seizures




Genotype
MGI:5521535
ht3
Allelic
Composition
Scn1atm1.1Kzy/Scn1a+
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Scn1atm1.1Kzy mutation (2 available); any Scn1a mutation (114 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 2 of 4 mice die within the third month after birth

behavior/neurological
• spontaneous epileptic seizures

nervous system
• spontaneous epileptic seizures





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
12/10/2024
MGI 6.24
The Jackson Laboratory