Phenotypes associated with this allele
Allelic Composition |
Ryr2tm1Slh/Ryr2+
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Genetic Background |
involves: 129S7/SvEvBrd |
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ryr2tm1Slh mutation
(0 available);
any
Ryr2 mutation
(325 available)
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cardiovascular system
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• atrial pacing using atrial burst results in increased ectopic beats and reentry compared to in similarly treated wild-type mice
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• atria myocyte exhibit increased sarcoplasmic reticulum calcium ion leak compared with wild-type cells
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• mice are more susceptible to pacing-induced atrial fibrillation compared with similarly treated wild-type mice
• however, the increased susceptibility to pacing-induced atrial fibrillation can be rescued by over-expression of Adcy3 inhibitory peptide
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homeostasis/metabolism
Allelic Composition |
Ryr2tm1Slh/Ryr2+
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Genetic Background |
involves: 129S7/SvEvBrd * C57BL/6 |
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ryr2tm1Slh mutation
(0 available);
any
Ryr2 mutation
(325 available)
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Ryr2tm1Slh/Ryr+ MRI heart images
cardiovascular system
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• systolic function is modestly reduced as demonstrated by decreased peak of aortic velocity
• exhibit a lowered right ventricular end-diastolic volume and higher right ventricular end-diastolic pressure, indicating restrictive ventricular filling, however show no evidence of fibrofatty infiltration or arrhythmogenic right ventricular dysplasia
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• develop ventricular tachycardia after caffeine and epinephrine injection or with programmed ventricular stimulation
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• multiple premature ventricular beats are seen after isoproterenol treatment (a beta-adrenergic receptor agonist), however no sustained ventricular arrhythmias are seen
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• isolated cardiomyocytes exhibit a higher incidence of spontaneous calcium oscillations in the absence and presence of isoproterenol
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muscle
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• systolic function is modestly reduced as demonstrated by decreased peak of aortic velocity
• exhibit a lowered right ventricular end-diastolic volume and higher right ventricular end-diastolic pressure, indicating restrictive ventricular filling, however show no evidence of fibrofatty infiltration or arrhythmogenic right ventricular dysplasia
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Allelic Composition |
Ryr2tm1Slh/Ryr2+
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Genetic Background |
involves: 129S7/SvEvBrd * C57BL/6J |
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ryr2tm1Slh mutation
(0 available);
any
Ryr2 mutation
(325 available)
|
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behavior/neurological
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• 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
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mortality/aging
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• 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
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cardiovascular system
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• 3 of 5 mice show spontaneous episodes of bradycardia and artrioventricular block
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• lethal cardiac arrhythmias occur after seizures are induced
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• mice injected with a high dose of caffeine show abnormal EKG patterns characterized by frequent bigeminy and sporadic ventricular fibrillation
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• 3 of 5 mice show spontaneous episodes of bradycardia and artrioventricular block
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• 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
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nervous system
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• 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
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• mice show lowered threshold for spreading depolarization in the neocortex and the brainstem dorsal medulla which leads to cardiorespiratory collapse
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• 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
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• 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
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• 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
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• the paired pulse ratio is reduced and less variable in pyramidal neurons
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