Phenotypes Associated with This Genotype

Genotype
MGI:6188940

• Allelic Composition: Tg(Myh6-Pkp2*/mRuby)4Rbrug/0; Tg(Myh6-Pkp2*/mRuby)5Rbrug/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

cardiovascular system

abnormal intercalated disk morphology ( J:237859 )

• intercalated disk shows gaps between both membranes with loss of cell-to-cell adhesion and eventually complete rupture of the disks

• defects in desmosome integrity, with 10 month old mice showing desmosome disassembly and adhesion reduction

abnormal heart right ventricle outflow tract morphology ( J:237859 )

• right ventricle outflow tract is dilated at 7 and 12 months of age

decreased heart left ventricle muscle contractility ( J:237859 )

• decrease in left ventricle shortening at 7 and 12 months of age

abnormal heart echocardiography feature ( J:237859 )

• echocardiography of 7 month old sedentary mice shows a reduction in left ventricle systolic function, with decreased left ventricle fractional shortening, and changes in right ventricle function and structure

• right ventricle systolic dysfunction, likely leading to a decreased ability to raise pulmonary pressure

ventricular tachycardia ( J:237859 )

• electrical programmed stimulation induces ventricular tachycardia in 74% of sedentary mice compared to 31% of wild-type mice indicating increased susceptibility to ventricular arrhythmias

• however, no differences are seen in training-dependent arrhythmia induction

abnormal impulse conducting system conduction ( J:237859 )

• atrio-ventricular conduction assessment shows a progressive prolongation of the Atrial-His conduction (A-H interval)

prolonged PR interval ( J:237859 )

• in 3, 7, and 12 month old mice

prolonged QRS complex duration ( J:237859 )

• prolonged QRS in 3, 7, and 12 month old mice

• however, no differences in heart rate, P-wave or QTc duration are seen

cardiomyopathy ( J:237859 )

• aged mice develop arrhythmogenic cardiomyopathy

• however, however, mice do not exhibit cardiac hypertrophy and no evidence of collagen deposition or fatty tissue replacement in the heart

muscle

abnormal intercalated disk morphology ( J:237859 )

• intercalated disk shows gaps between both membranes with loss of cell-to-cell adhesion and eventually complete rupture of the disks

• defects in desmosome integrity, with 10 month old mice showing desmosome disassembly and adhesion reduction

decreased heart left ventricle muscle contractility ( J:237859 )

• decrease in left ventricle shortening at 7 and 12 months of age

cardiomyopathy ( J:237859 )

• aged mice develop arrhythmogenic cardiomyopathy

• however, however, mice do not exhibit cardiac hypertrophy and no evidence of collagen deposition or fatty tissue replacement in the heart

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arrhythmogenic right ventricular dysplasia 9		DOID:0110077	OMIM:609040	J:237859