Phenotypes associated with this allele

• Allele Symbol: Ank2^em1Melr
• Allele Name: endonuclease-mediated mutation 1, Mona El Refaey
• Allele ID: MGI:7513830
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ank2^em1Melr/Ank2^em1Melr	B6.Cg-Ank2^em1Melr	MGI:7514498

Genotype
MGI:7514498

hm1

• Allelic Composition: Ank2^em1Melr/Ank2^em1Melr
• Genetic Background: B6.Cg-Ank2^em1Melr

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

cardiovascular system

cardiac fibrosis ( J:338515 )

• 6-month-old mice show widespread cardiac fibrosis

• young mice exhibit widespread cardiac fibrosis at 8 and 12 weeks post transverse aortic constriction

decreased cardiac muscle contractility ( J:338515 )

• mice show a reduction in ejection fraction and fractional shortening around 6 months of age but not at 3 months of age

• young mice exhibit a reduction in contractility, ejection fraction, and fractional shortening at 8 and 12 weeks post transverse aortic constriction

abnormal heart echocardiography feature ( J:338515 )

• mice show a reduction in ejection fraction and fractional shortening and a trend towards an increased left ventricular internal diameter (LVID) and decreased left ventricular posterior wall (LVPW) during systole at 6 months of age

• however, no changes in LVID or LVPW during diastole are seen and mice do not show left ventricular dilatation

decreased heart rate ( J:338515 )

• the high frequency and low frequency spectral components of heart rate variability are increased at rest indicating mild bradycardia

• the high frequency/low frequency ratio is reduced

prolonged RR interval ( J:338515 )

• the RR interval is prolonged at 6 months of age

• however, no changes are seen in the P wave duration, PR interval, or the QRS duration

sinus bradycardia ( J:338515 )

• conscious 6-month-old mice exhibit sinus bradycardia at rest

irregular heartbeat ( J:338515 )

• mice show arrhythmic events following adrenergic challenge or acute stressor at an early age,with events becoming more severe and sustained in adults at 6 months of age

prolonged QT interval ( J:338515 )

• 6-month-old mice show prolonged QT interval

• however, the corrected QT interval only trends toward prolongation and does not reach statistical significance

abnormal myocardial fiber physiology ( J:338515 )

• cardiac myocytes treated with isoproterenol show a higher predisposition to calcium transient alternans than wild-type myocytes, indicating calcium handling dysfunction in myocytes

• however, cardiac myocytes treated with isoproterenol show a similar increase in amplitude and rate of decay of calcium transients and similar frequency of spontaneous calcium waves as controls

increased response of heart to induced stress ( J:338515 )

• both young and 6-month-old mice show an increase in the number of ventricular arrhythmic events when challenged with epinephrine

• 6-month-old mice challenged with a stress protocol consisting of combined epinephrine and caffeine show an increase in the number of ventricular arrhythmic events and a higher number and prolonged duration of sustained episodes of ventricular tachycardia while the number of non-sustained ventricular tachycardia episodes trends upward

• mice show arrhythmic events following adrenergic challenge or acute stressor at an early age,with events becoming more severe and sustained in adults at 6 months of age

• young mice develop severe cardiac phenotypes in response to chronic cardiac pressure overload

• mice exhibit a reduction in contractility, ejection fraction, and fractional shortening, and widespread cardiac fibrosis at 8 and 12 weeks post transverse aortic constriction, however mice do not show differences in left ventricular internal diameter (LVID) during diastole or systole from controls post transverse aortic constriction

homeostasis/metabolism

increased response of heart to induced stress ( J:338515 )

• both young and 6-month-old mice show an increase in the number of ventricular arrhythmic events when challenged with epinephrine

• 6-month-old mice challenged with a stress protocol consisting of combined epinephrine and caffeine show an increase in the number of ventricular arrhythmic events and a higher number and prolonged duration of sustained episodes of ventricular tachycardia while the number of non-sustained ventricular tachycardia episodes trends upward

• mice show arrhythmic events following adrenergic challenge or acute stressor at an early age,with events becoming more severe and sustained in adults at 6 months of age

• young mice develop severe cardiac phenotypes in response to chronic cardiac pressure overload

• mice exhibit a reduction in contractility, ejection fraction, and fractional shortening, and widespread cardiac fibrosis at 8 and 12 weeks post transverse aortic constriction, however mice do not show differences in left ventricular internal diameter (LVID) during diastole or systole from controls post transverse aortic constriction

muscle

decreased cardiac muscle contractility ( J:338515 )

• mice show a reduction in ejection fraction and fractional shortening around 6 months of age but not at 3 months of age

• young mice exhibit a reduction in contractility, ejection fraction, and fractional shortening at 8 and 12 weeks post transverse aortic constriction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ankyrin-B-related cardiac arrhythmia		DOID:0111700	OMIM:600919	J:338515