Phenotypes Associated with This Genotype

Genotype
MGI:5296512

• Allelic Composition: Jup^tm1.1Shou/Jup^tm1.1Shou; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129 * C57BL/6J

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

mortality/aging

premature death ( J:177567 )

• mutants suddenly die starting at 1 month of age, with an average life-span of 4.6 months

cardiovascular system

liver vascular congestion ( J:177567 )

• mutants exhibit severe liver congestion

abnormal myocardial fiber morphology ( J:177567 )

• cardiomyocytes are hypertrophic, showing an increase in cross-sectional area

• hearts show loss of desmosomes, however adherens junctions are normal

calcified myocardium ( J:177567 )

• myocardial calcification is seen in 2-month old ventricles

cardiac muscle necrosis ( J:177567 )

• 18 day old mutants exhibit extensive cardiomyocyte death, including apoptisis and necrosis

increased heart right atrium size ( J:177567 )

enlarged heart ( J:177567 )

• heart is enlarged at 2 months of age

abnormal heart ventricle morphology ( J:177567 )

• hearts exhibit regional dysplasia of ventricular walls and ventricular aneurysms

ventricular aneurysm ( J:177567 )

cardiac fibrosis ( J:177567 )

• cardiac fibrosis is seen in atria and ventricles; fibrosis ranges from moderate to severe

dilated heart ( J:177567 )

dilated heart right ventricle ( J:177567 )

abnormal cardiovascular system physiology ( J:177567 )

• ECG shows compromised systolic function of the left ventricle

• fragmented diastolic potentials are seen in right ventricle

decreased cardiac muscle contractility ( J:177567 )

• hearts show reduced fractional shortening and ejection fraction

ventricular tachycardia ( J:177567 )

• at 1 and 2 months of age, mutants exhibit spontaneous non-sustained ventricular tachycardia

• sustained monomorphic ventricular tachycardias are induced in mutants by bust or programmed ventricular stimulation in 6 of 7 mutants but not in controls

• mutants exhibit intracardiac bipolar electrograms during ventricular tachycardia

abnormal impulse conducting system conduction ( J:177567 )

• in Langendorff-perfused hearts, conduction velocity max and min are reduced

abnormal heart electrocardiography waveform feature ( J:177567 )

• at 1 month of age, mutants exhibit complex electrophysiological abnormalities, with low amplitude of the QRS complex, prolonged PR interval and spontaneous non-sustained ventricular tachycardia

• by 2 months of age, the amplitude of the P-wave is higher, amplitude of QRS complex is lower, the PR interval is prolonged, and frequent spontaneous ventricular ectopic beats are seen

prolonged PR interval ( J:177567 )

• at 1 and 2 months of age, mutants exhibit prolonged PR interval

abnormal P wave ( J:177567 )

• by 2 months of age, the amplitude of the P-wave is higher

decreased QRS amplitude ( J:177567 )

• ECG shows decreased QRS complex amplitude at P18, 1 month and 2 months of age

cardiomyopathy ( J:177567 )

• mutants show rapid and progressive development of cardiomyopathy; hearts appear normal at P12 but by P18, show signs of fibrosis and heart enlargement by 1 month

liver/biliary system

liver vascular congestion ( J:177567 )

• mutants exhibit severe liver congestion

muscle

abnormal myocardial fiber morphology ( J:177567 )

• cardiomyocytes are hypertrophic, showing an increase in cross-sectional area

• hearts show loss of desmosomes, however adherens junctions are normal

calcified myocardium ( J:177567 )

• myocardial calcification is seen in 2-month old ventricles

cardiac muscle necrosis ( J:177567 )

• 18 day old mutants exhibit extensive cardiomyocyte death, including apoptisis and necrosis

decreased cardiac muscle contractility ( J:177567 )

• hearts show reduced fractional shortening and ejection fraction

cardiomyopathy ( J:177567 )

• mutants show rapid and progressive development of cardiomyopathy; hearts appear normal at P12 but by P18, show signs of fibrosis and heart enlargement by 1 month

increased cardiomyocyte apoptosis ( J:177567 )

• 18 day old mutants exhibit extensive cardiomyocyte death, including apoptisis and necrosis

cellular

increased cardiomyocyte apoptosis ( J:177567 )

• 18 day old mutants exhibit extensive cardiomyocyte death, including apoptisis and necrosis

growth/size/body

enlarged heart ( J:177567 )

• heart is enlarged at 2 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arrhythmogenic right ventricular dysplasia 12		DOID:0110083	OMIM:611528	J:177567