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Phenotypes Associated with This Genotype
Genotype
MGI:6278119
Allelic
Composition
Ryr2tm1Slh/Ryr2+
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ryr2tm1Slh mutation (0 available); any Ryr2 mutation (39 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• juvenile mice show increased susceptibility to 4-aminopyridine induced seizures and to seizure-induced lethality, likely due to hypoxia/hypoxemia resulting from peri-ictal cardiorespiratory instability and a lower threshold for spreading depolarization and to seizure-induced lethality, likely due to hypoxia/hypoxemia resulting from peri-ictal cardiorespiratory instability and a lower threshold for spreading depolarization

mortality/aging
• all mice injected with a high dose of caffeine die within 2 hours of post-injection, indicating caffeine-induced lethal cardiac arrhythmias
• 71% of mice die shortly after 4-aminopyridine-induced seizures

cardiovascular system
• 3 of 5 mice show spontaneous episodes of bradycardia and artrioventricular block
• lethal cardiac arrhythmias occur after seizures are induced
• mice injected with a high dose of caffeine show abnormal EKG patterns characterized by frequent bigeminy and sporadic ventricular fibrillation
• 3 of 5 mice show spontaneous episodes of bradycardia and artrioventricular block
• prolonged EEG-EKG monitoring indicates spontaneous bilateral cortical epileptiform spike discharges
• mice injected with a high dose of caffeine show abnormal EKG patterns characterized by frequent bigeminy and sporadic ventricular fibrillation

nervous system
• juvenile mice show increased susceptibility to 4-aminopyridine induced seizures and to seizure-induced lethality, likely due to hypoxia/hypoxemia resulting from peri-ictal cardiorespiratory instability and a lower threshold for spreading depolarization and to seizure-induced lethality, likely due to hypoxia/hypoxemia resulting from peri-ictal cardiorespiratory instability and a lower threshold for spreading depolarization
• mice show lowered threshold for spreading depolarization in the neocortex and the brainstem dorsal medulla which leads to cardiorespiratory collapse
• pyramidal neurons show an increase in slow after-hyperpolarization following an evoked action potential train
• however, no differences in resting membrane potential, resistance, or action potential frequency to injected depolarizing currents are seen
• prolonged EEG-EKG monitoring indicates spontaneous bilateral cortical epileptiform spike discharges
• abnormal spike discharges are mostly absent when mice are behaviorally active and increase at rest
• cortical theta power (4-7Hz) is increased during spike-frequent periods compared to spike-free periods
• seizure activity is rare
• the paired pulse ratio is reduced and less variable in pyramidal neurons
• mean miniature excitatory postsynaptic current (mEPSC) amplitude is larger in cortical layer II/III neurons, however frequency is not different
• mEPSC amplitude is increased in dorsal motor vagal neurons, however the mean frequency is unchanged
• however, layer II/III pyramidal neurons show normal spontaneous excitatory postsynaptic current frequency and amplitude

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
catecholaminergic polymorphic ventricular tachycardia 1 DOID:0060675 OMIM:604772
J:235432


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
07/09/2019
MGI 6.14
The Jackson Laboratory