Phenotypes associated with this allele
|
Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ryr2tm2Amks mutation
(1 available);
any
Ryr2 mutation
(325 available)
|
|
|
mortality/aging
|
• despite normal numbers at E13.5, fewer than expected mice are present at E16.5
• however, treatment of mothers with S107 (a 1,4-benzothiazepine) rescues lethality of pups
|
nervous system
|
• in two of the few surviving mice
|
growth/size/body
behavior/neurological
|
• in two of the few surviving mice
|
|
Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ryr2tm2Amks mutation
(1 available);
any
Ryr2 mutation
(325 available)
|
|
|
mortality/aging
|
• following strenuous exercise and catecholamine injection, mice exhibit sudden cardiac death unlike wild-type mice
• however, sudden cardiac death is not associated with seizures and treatment with S107 (a 1,4-benzothiazepine) can reduce this response to strenuous exercise and catecholamine injection
|
nervous system
N |
• despite the occurrence of seizures, brain histology is normal
|
|
• mice begin to exhibit spontaneous and recurrent seizures during weaning (P21 to P28)
• mice exhibit generalized clonic-tonic seizures in response to being placed in a new cage, woken from sleep or without any external stimuli
• seizures are associated with high-frequency calcium ion signaling and or burst activity
|
|
• during seizures, mice exhibit rapid spike discharges
|
cardiovascular system
|
• following strenuous exercise and catecholamine injection, mice exhibit ventricular tachycardia and sudden cardiac death unlike wild-type mice
|
|
• cardiomyocytes stimulated with isoproterenol exhibit delayed afterdepolarizations between pacing cycles unlike in similarly treated wild-type mice that increases the depolarization rate from 1 Hz to 3 Hz and decreased coupling interval causing action potential fusion, incomplete repolarization, and spontaneous pacemaker activity
• cardiomyocytes treated with isoproterenol exhibit aberrant calcium ion transients between regular field-stimulated calcium ion transients that become self-sustaining unlike in similarly treated wild-type mice
|
|
• following strenuous exercise and catecholamine injection, mice exhibit ventricular tachycardia and sudden cardiac death unlike wild-type mice
• however, ventricular tachycardia and sudden cardiac death is not associated with seizures and treatment with S107 (a 1,4-benzothiazepine) can reduce these responses to strenuous exercise and catecholamine injection
• following strenuous exercise and catecholamine injection, mice exhibit an open probability that is higher than in sedentary mice that can be reversed with treatment with S107
|
behavior/neurological
|
• mice begin to exhibit spontaneous and recurrent seizures during weaning (P21 to P28)
• mice exhibit generalized clonic-tonic seizures in response to being placed in a new cage, woken from sleep or without any external stimuli
• seizures are associated with high-frequency calcium ion signaling and or burst activity
|
homeostasis/metabolism
Allelic Composition |
Ryr2tm2Amks/Ryr2+
|
|
Genetic Background |
involves: 129S1/Sv * 129X1/SvJ |
|
Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ryr2tm2Amks mutation
(1 available);
any
Ryr2 mutation
(325 available)
|
|
|
cardiovascular system
|
• leaky calcium channels in the sarcoplasmic reticulum of atrial myocytes
• however, a 1,4-benzothiazepine (Rycal S107) prevents calcium leak
|
|
• induced by atrial burst pacing in 7 of 10 mice
• however, a 1,4-benzothiazepine (Rycal S107) prevents atrial burst pacing-induced atrial fibrillation
|
muscle
|
• leaky calcium channels in the sarcoplasmic reticulum of atrial myocytes
• however, a 1,4-benzothiazepine (Rycal S107) prevents calcium leak
|
|
• leaky calcium channels in the sarcoplasmic reticulum of atrial and, to a lesser extent, ventricular myocytes
• however, a 1,4-benzothiazepine (Rycal S107) prevents calcium leak
|