Phenotypes associated with this allele

• Allele Symbol: Ryr2^em1Swch
• Allele Name: endonuclease-mediated mutation 1, S R Wayne Chen
• Allele ID: MGI:6682022
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ryr2^em1Swch/Ryr2^em1Swch	involves: 129 * C57BL/6	MGI:6682029
ht2	Ryr2^em1Swch/Ryr2^+	involves: 129 * C57BL/6	MGI:6682030

Genotype
MGI:6682029

hm1

• Allelic Composition: Ryr2^em1Swch/Ryr2^em1Swch
• Genetic Background: involves: 129 * C57BL/6

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

mortality/aging

prenatal lethality, complete penetrance ( J:302151 )

• no homozygotes are produced, suggesting embryonic lethality

Genotype
MGI:6682030

ht2

• Allelic Composition: Ryr2^em1Swch/Ryr2⁺
• Genetic Background: involves: 129 * C57BL/6

cardiovascular system

abnormal heart echocardiography feature ( J:302151 )

• echocardiography shows a slightly reduced heart rate of about 10% and moderately increased (about 20%) left ventricular wall thickness

• however, ejection fraction, fractional shortening, stroke volume and cardiac output are unchanged

decreased heart rate ( J:302151 )

• heart rate is reduced about 10%

irregular heartbeat ( J:302151 )

• none of the common stimulation protocols (a burst pacing, a long pause, and a short-coupled premature ventricular complex) reliably induce ventricular arrhythmias in mutant mice

• however, a protocol consisting of a long-burst, long-pause, and short-coupled extra-stimulus (LBLPS) consistently triggers ventricular arrhythmias in mutants but not wild-type mice

• mice pretreated with quinidine sulfate reduces the duration and incidence of LBLPS-evoked polymorphic ventricular arrhythmias

abnormal myocardial fiber physiology ( J:302151 )

• elevating extracellular calcium concentration to promote sarcoplasmic reticulum calcium overload, induces little or no calcium waves in hearts

• hearts show resilience to caffeine- and epinephrine-promoted spontaneous calcium waves

• at high stimulation frequencies, hearts are more prone to calcium alternans and exhibit prolonged calcium release refractoriness

• however, the amplitude, time to peak, and decay time of depolarization-induced calcium transients at low stimulation frequency in hearts or isolated cardiomyocytes are similar to wild-type mice

• ventricular myocytes show an electrophysiological remodeling of surface membrane currents

• the Na/Ca exchange current is substantially augmented in ventricular myocytes

• the transient outward potassium current density and voltage-dependent activation are enhanced in ventricular myocytes

• ventricular myocytes are highly susceptible to early afterdepolarizations

abnormal myocardial fiber calcium currents ( J:302151 )

• L-type calcium channel current density in ventricular myocytes is enhanced

abnormal myocardial fiber sodium currents ( J:302151 )

• the sodium current shows a leftward (hyperpolarization) shift in voltage-dependent activation and inactivation in ventricular myocytes

decreased response of heart to induced stress ( J:302151 )

• a mixture of a high dose of caffeine and epinephrine does not promote ventricular arrhythmias as in wild-type mice, indicating protection of heart against stress-induced ventricular arrhythmias

homeostasis/metabolism

decreased response of heart to induced stress ( J:302151 )

• a mixture of a high dose of caffeine and epinephrine does not promote ventricular arrhythmias as in wild-type mice, indicating protection of heart against stress-induced ventricular arrhythmias

nervous system

abnormal action potential ( J:302151 )

• ventricular myocytes exhibit an altered action potential waveform with a shorter action potential duration at 50% and prolonged action potential duration at 90%, however the action potential amplitude and resting membrane potential are unchanged

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
heart disease		DOID:114		J:302151