Phenotypes associated with this allele

• Allele Symbol: Ryr2^tm2Amks
• Allele Name: targeted mutation 2, Andrew R Marks
• Allele ID: MGI:3802940
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ryr2^tm2Amks/Ryr2^tm2Amks	B6.129-Ryr2^tm2Amks	MGI:3803483
ht2	Ryr2^tm2Amks/Ryr2^+	B6.129-Ryr2^tm2Amks	MGI:3803484
ht3	Ryr2^tm2Amks/Ryr2^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5582595

Genotype
MGI:3803483

hm1

• Allelic Composition: Ryr2^tm2Amks/Ryr2^tm2Amks
• Genetic Background: B6.129-Ryr2^tm2Amks

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

mortality/aging

decreased survivor rate ( J:137696 )

• very few mice survive

lethality throughout fetal growth and development, incomplete penetrance ( J:137696 )

• 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

increased susceptibility to pharmacologically induced seizures ( J:137696 )

tonic-clonic seizures ( J:137696 )

• in two of the few surviving mice

growth/size/body

fetal growth retardation ( J:137696 )

• at E16.5

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:137696 )

tonic-clonic seizures ( J:137696 )

• in two of the few surviving mice

Genotype
MGI:3803484

ht2

• Allelic Composition: Ryr2^tm2Amks/Ryr2⁺
• Genetic Background: B6.129-Ryr2^tm2Amks

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:137696 )

• 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

nervous system phenotype ( J:137696 )

N • despite the occurrence of seizures, brain histology is normal

increased susceptibility to pharmacologically induced seizures ( J:137696 )

tonic-clonic seizures ( J:137696 )

• 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

abnormal brain wave pattern ( J:137696 )

• during seizures, mice exhibit rapid spike discharges

cardiovascular system

ventricular tachycardia ( J:137696 )

• following strenuous exercise and catecholamine injection, mice exhibit ventricular tachycardia and sudden cardiac death unlike wild-type mice

abnormal myocardial fiber physiology ( J:137696 )

• 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

increased response of heart to induced stress ( J:137696 )

• 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

increased susceptibility to pharmacologically induced seizures ( J:137696 )

tonic-clonic seizures ( J:137696 )

• 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

increased response of heart to induced stress ( J:137696 )

• 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

Genotype
MGI:5582595

ht3

• Allelic Composition: Ryr2^tm2Amks/Ryr2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

cardiovascular system

abnormal myocardial fiber morphology ( J:212640 )

• leaky calcium channels in the sarcoplasmic reticulum of atrial myocytes

• however, a 1,4-benzothiazepine (Rycal S107) prevents calcium leak

atrial fibrillation ( J:212640 )

• 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

abnormal myocardial fiber morphology ( J:212640 )

• leaky calcium channels in the sarcoplasmic reticulum of atrial myocytes

• however, a 1,4-benzothiazepine (Rycal S107) prevents calcium leak

abnormal sarcoplasmic reticulum morphology ( J:212640 )

• 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

cellular

abnormal sarcoplasmic reticulum morphology ( J:212640 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
catecholaminergic polymorphic ventricular tachycardia 1		DOID:0060675	OMIM:604772	J:212640