Phenotypes associated with this allele

• Allele Symbol: Ryr2^tm2.1Wex
• Allele Name: targeted mutation 2.1, Xander Wehrens
• Allele ID: MGI:5571850
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ryr2^tm2.1Wex/Ryr2^tm2.1Wex	B6.129S7-Ryr2^tm2.1Wex	MGI:5571851
hm2	Ryr2^tm2.1Wex/Ryr2^tm2.1Wex	involves: 129S7/SvEvBrd	MGI:5571875
cx3	Ryr2^tm2.1Wex/Ryr2^tm2.1Wex Tg(Myh6-EGFP/AC3I)#Mean/0	B6.Cg-Ryr2^tm2.1Wex Tg(Myh6-EGFP/AC3I)#Mean	MGI:5571853

Genotype
MGI:5571851

hm1

• Allelic Composition: Ryr2^tm2.1Wex/Ryr2^tm2.1Wex
• Genetic Background: B6.129S7-Ryr2^tm2.1Wex

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:179475 )

• mice subjected to transverse aortic constriction exhibit ventricular arrhythmias immediately preceding death unlike wild-type mice

cardiovascular system

cardiovascular system phenotype ( J:179475 )

N • normal basal cardiac morphology at 3 months of age and heart rhythm at rest

abnormal myocardial fiber morphology ( J:179475 )

• at baseline, calcium spark frequency is increased compared to in wild-type myocytes

• following endogenous Camk2 activation, no additional effect pm calcium spark frequency unlike wild-type cells

• the time constant of twitch intracellular calcium concentration is lower than in wild-type cells

• sarcoplasmic reticulum calcium load is lower than in wild-type cells

• myocytes exhibit enhanced fractional sarcoplasmic reticulum calcium release induced by caffeine compared with wild-type cells

abnormal heart left ventricle morphology ( J:179475 )

• increased left ventricle posterior wall diameter and end-diastolic diameter at 12 months

decreased cardiac muscle contractility ( J:179475 )

• at 12 months

decreased heart rate ( J:179475 )

• after treatment with caffeine and epinephrine, ventricular tachycardia deteriorates into bradycardia and then asystole

ventricular tachycardia ( J:179475 )

• after treatment with caffeine and epinephrine, ventricular tachycardia deteriorates into bradycardia and then asystole

• burst pacing evoked sustained ventricular tachycardia in more mice than in wild-type mice

• mice subjected to transverse aortic constriction exhibit ventricular arrhythmias immediately preceding death unlike wild-type mice

• however, treatment with propranolol does not affect ventricular arrhythmia induction

absent heartbeat ( J:179475 )

• after treatment with caffeine and epinephrine, ventricular tachycardia deteriorates into bradycardia and then asystole

ventricular premature beat ( J:179475 )

• in mice challenged with isoproterenol

increased response of heart to induced stress ( J:179475 )

• mice subjected to transverse aortic constriction exhibit ventricular arrhythmias immediately preceding death unlike wild-type mice

homeostasis/metabolism

increased response of heart to induced stress ( J:179475 )

• mice subjected to transverse aortic constriction exhibit ventricular arrhythmias immediately preceding death unlike wild-type mice

muscle

abnormal myocardial fiber morphology ( J:179475 )

• at baseline, calcium spark frequency is increased compared to in wild-type myocytes

• following endogenous Camk2 activation, no additional effect pm calcium spark frequency unlike wild-type cells

• the time constant of twitch intracellular calcium concentration is lower than in wild-type cells

• sarcoplasmic reticulum calcium load is lower than in wild-type cells

• myocytes exhibit enhanced fractional sarcoplasmic reticulum calcium release induced by caffeine compared with wild-type cells

decreased cardiac muscle contractility ( J:179475 )

• at 12 months

Genotype
MGI:5571875

hm2

• Allelic Composition: Ryr2^tm2.1Wex/Ryr2^tm2.1Wex
• Genetic Background: involves: 129S7/SvEvBrd

muscle

abnormal sarcoplasmic reticulum morphology ( J:210426 )

• higher basal calcium spark frequency and lower sarcoplasmic calcium load that is not modulated by 8-CPT

• however, baseline calcium transient amplitudes are normal

Genotype
MGI:5571853

cx3

• Allelic Composition: Ryr2^tm2.1Wex/Ryr2^tm2.1Wex; Tg(Myh6-EGFP/AC3I)#Mean/0
• Genetic Background: B6.Cg-Ryr2^tm2.1Wex Tg(Myh6-EGFP/AC3I)#Mean

cardiovascular system

ventricular tachycardia ( J:179475 )

• that is slightly less than in Ryr2^tm2.1Wex homozygotes

• incidence of tachycardia in isoproterenol-treated mice is the same as in Ryr2^tm2.1Wex homozygotes