Phenotypes Associated with This Genotype

Genotype
MGI:4443207

• Allelic Composition: Ryr2^tm1.1Maya/Ryr2⁺
• Genetic Background: C57BL/6J-Ryr2^tm1.1Maya

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

cardiovascular system

ventricular tachycardia ( J:159451 )

• mice exhibit polymorphic ventricular premature contractions in response to light or sound unlike wild-type mice

• mice exposed to exercise or treatment with caffeine plus epinephrine exhibit bidirectional or polymorphic ventricular tachycardia unlike similarly treated wild-type mice

abnormal myocardial fiber physiology ( J:159451 )

• cardiomyocytes from mice treated with isoproterenol exhibit an 80% decline in peak cell shortening and prolonged calcium ion transient compared with cardiomyocytes form similarly treated wild-type mice

• before or after treatment with isoproterenol, sarcoplasmic reticulum calcium ion content is less than in cardiomyocytes from similarly treated wild-type mice

• before or after treatment with isoproterenol, calcium ion spark frequency is higher than in cardiomyocytes from similarly treated wild-type mice

• mice treated with 100 nmol/L isoproterenol exhibit higher frequencies of spontaneous calcium ion waves and increased full duration at half maximum compared with similarly treated wild-type mice

• cardiomyocytes exhibit decreased free diastolic sarcoplasmic reticulum calcium ions compared with wild-type cells

• however, luminal calcium ion levels reach the same baseline as in wild-type mice after caffeine treatment and treatment with dantrolene abolishes abnormal spontaneous after potentials and calcium ion transients following treatment with isoproterenol

• after isoproterenol treatment, cardiomyocytes exhibit spontaneous calcium ion transients and spontaneous after potentials unlike similarly treated wild-type cells

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:159451 )

• mice exposed to exercise or treatment with caffeine plus epinephrine exhibit bidirectional or polymorphic ventricular tachycardia unlike similarly treated wild-type mice

• cardiomyocytes from mice treated with isoproterenol exhibit a decrease in time from peak to 80% decline in cell shortening and prolonged calcium ion transient compared with cardiomyocytes form similarly treated wild-type mice

• mice treated with 100 nmol/L isoproterenol exhibit higher frequencies of spontaneous calcium ion waves and increased full duration at half maximum compared with similarly treated wild-type mice

• after isoproterenol treatment, cardiomyocytes exhibit spontaneous calcium ion transients and spontaneous after potentials unlike similarly treated wild-type cells

• however, treatment with dantrolene abolishes abnormal spontaneous after potentials and calcium ion transients following treatment with isoproterenol

behavior/neurological

behavior/neurological phenotype ( J:159451 )

N • unlike Ryr2^tm2Amks homozygotes, mice do not exhibit spontaneous seizures or increased susceptibility to pharmacologically induced seizures following treatment with 4-aminopyridine and caffeine compared with wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
catecholaminergic polymorphic ventricular tachycardia 1		DOID:0060675	OMIM:604772	J:159451