Phenotypes associated with this allele

• Allele Symbol: Rangrf^tm1.1Tke
• Allele Name: targeted mutation 1.1, Tie Ke
• Allele ID: MGI:7386934
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rangrf^tm1.1Tke/Rangrf^tm1.1Tke	involves: C57BL/6	MGI:7387041

Genotype
MGI:7387041

hm1

• Allelic Composition: Rangrf^tm1.1Tke/Rangrf^tm1.1Tke
• Genetic Background: involves: C57BL/6

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

cardiovascular system

abnormal cardiac muscle tissue morphology ( J:325055 )

• focal lysis of cardiac muscle fibers

• however, no obvious inflammation or fat accumulation are seen in the heart, no differences are noted in body weight, heart weight, or heart weight to body weight ratios, and no signs of cardiac enlargement, ventricular dilation or hypertrophy are seen

abnormal myocardial fiber morphology ( J:325055 )

• cardiac myofibrils are partially disordered, loose, ruptured and lysed in 6-month-old mice

• however, endoplasmic reticulum structure is normal

abnormal heart ventricle morphology ( J:325055 )

• abnormal mitochondrial morphology in cardiac ventricles, including cristae disarrangement, partial cristolysis, increased vacuoles, and a minor degree of severe membrane damage and disintegration of mitochondria

• average size of mitochondria are increased and there is an increase in the number of large mitochondria

cardiac fibrosis ( J:325055 )

• increase in ventricular fibrosis at 6 months of age

abnormal cardiovascular system physiology ( J:325055 )

• dye transfer assays on heart tissue show that dye transfer distance is reduced by 39%, indicating reduced gap junction permeability

• however, no changes in cardiac sodium channel current or action potential duration in ventricular myocytes are seen

decreased cardiac muscle contractility ( J:325055 )

• ejection fraction and fractional shortening are reduced indicating attenuated cardiac contractile function

abnormal heart echocardiography feature ( J:325055 )

• echocardiography shows enlarged left ventricle end-diastolic diameter and left ventricle end-systolic diameter, and reduced ejection fraction and fractional shortening

ventricular tachycardia ( J:325055 )

• 3 of 6 isoproterenol-treated mice develop ventricular tachycardia and sudden cardiac death from arrest

ventricular premature beat ( J:325055 )

• telemetry ECG under conscious conditions shows that 2 of 8 mice at 6 months of age display premature ventricular contractions at a rate of 60-80 beats per hour

• mice treated with the beta-receptor agonist isoproterenol, show a higher incidence of premature ventricular contractions

atrioventricular block ( J:325055 )

• 4 of 6 isoproterenol-treated mice show AV block (class I, II, III)

prolonged QRS complex duration ( J:325055 )

• mice show prolongation of QRS duration until 6 months of age and QRS prolongation is still significant at 12 months of age

• however, other ECG parameters, including heart rate, RR interval, P wave duration, PR interval, and QTc interval show no differences and no obvious arrhythmic events are seen

cellular

disorganized mitochondrial cristae ( J:325055 )

• cristae disarrangement in cardiac ventricles

increased mitochondrial number ( J:325055 )

• increase in the number of large mitochondria

increased mitochondrial size ( J:325055 )

• average size of mitochondria is greater in cardiac ventricles

abnormal fibroblast physiology ( J:325055 )

• maker analysis of alpha-SMA expression indicates increased cardiac fibroblast activation

increased fibroblast proliferation ( J:325055 )

• marker analysis indicates a greater proliferative response of myocardial fibroblasts

abnormal mitochondrial physiology ( J:325055 )

• level of intracellular ATP is increased by 90%, indicating enhanced mitochondrial activity

abnormal mitochondrial biogenesis ( J:325055 )

• marker analysis suggests that dynamic balance between mitochondrial fission and fusion is disturbed with an increased trend toward mitochondrial fusion

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:325055 )

• 3 of 6 isoproterenol-treated mice develop ventricular tachycardia and sudden cardiac death from arrest

increased physiological sensitivity to xenobiotic ( J:325055 )

• mice treated with the beta-receptor agonist isoproterenol, show a higher incidence of premature ventricular contractions

• 4 of 6 isoproterenol-treated mice show atrioventricular (AV) block (class I, II, III)

• 3 of 6 isoproterenol-treated mice develop ventricular tachycardia and sudden cardiac death from arrest

• however, treatment with flecainide, a cardiac sodium channel blocker, shows no differences from wild-type mice

• administration of rotigaptide (ZP123), a specific Cx43 gap-junction enhancer, decreases arrhythmia inducibility in isoproterenol treated mice, with mice showing decreased incidence of premature ventricular contractions and atrioventricular block

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:325055 )

• 3 of 6 isoproterenol-treated mice develop ventricular tachycardia and sudden cardiac death from arrest

muscle

abnormal cardiac muscle tissue morphology ( J:325055 )

• focal lysis of cardiac muscle fibers

• however, no obvious inflammation or fat accumulation are seen in the heart, no differences are noted in body weight, heart weight, or heart weight to body weight ratios, and no signs of cardiac enlargement, ventricular dilation or hypertrophy are seen

abnormal myocardial fiber morphology ( J:325055 )

• cardiac myofibrils are partially disordered, loose, ruptured and lysed in 6-month-old mice

• however, endoplasmic reticulum structure is normal

decreased cardiac muscle contractility ( J:325055 )

• ejection fraction and fractional shortening are reduced indicating attenuated cardiac contractile function

abnormal sarcomere morphology ( J:325055 )

• mean cardiac sarcomere length is increased by 19%

abnormal I band morphology ( J:325055 )

• mean cardiac sarcomere I-band length is increased by 45%