Phenotypes associated with this allele

• Allele Symbol: Tg(Myh6-Pkp2*/mRuby)4Rbrug
• Allele Name: transgene insertion 4, Ramon Brugada
• Allele ID: MGI:6188930
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Myh6-Pkp2*/mRuby)4Rbrug/0 Tg(Myh6-Pkp2*/mRuby)5Rbrug/0	involves: C57BL/6 * DBA/2	MGI:6188940
tg2	Tg(Myh6-Pkp2*/mRuby)4Rbrug/0	involves: C57BL/6 * DBA/2	MGI:6188933

Genotype
MGI:6188940

cx1

• 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

Genotype
MGI:6188933

tg2

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

cardiovascular system

abnormal heart right ventricle morphology ( J:237859 )

• mice exhibit progressive structural right ventricle remodeling, with 12 month old mice showing right ventricle outflow tract and right ventricle diameter and area dilation

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

• 12 month old, but not 7 month old, mice show right ventricle outflow tract dilation

• long-term physical activity promotes right ventricle outflow tract dilation

dilated heart right ventricle ( J:237859 )

• mice show progressive right ventricle dilation from 7 to 12 months of age, indicating progressive structural remodeling

• endurance training and aging trigger right ventricular enlargement

• however, no changes in left ventricle structure and function are seen

abnormal heart echocardiography feature ( J:237859 )

• aged mice exhibit right ventricle dysfunction, with an increase in right ventricle end-diastolic area parasternal axis view and a decrease in tricuspid annular plane systolic excursion at 7 and 12 months of age

ventricular tachycardia ( J:237859 )

• electrical programmed stimulation induces ventricular tachycardia in 54% of sedentary mice compared to 31% of wild-type mice indicating increased susceptibility to ventricular arrhythmias

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

abnormal impulse conducting system conduction ( J:237859 )

• atrio-ventricular conduction assessment shows a prolongation of the Atrial-His conduction (A-H interval) in 7 month old mice

prolonged PR interval ( J:237859 )

• in 3, 7, and 12 month old mice

• 7 month old exercised trained mice show a greater PR interval prolongation than controls

cardiomyopathy ( J:237859 )

• aged mice develop mild arrhythmogenic cardiomyopathy

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

homeostasis/metabolism

abnormal response to exercise ( J:237859 )

• long-term physical activity promotes right ventricle outflow tract dilation and right ventricular enlargement

• however, exercise results in similar cardiac hypertrophy and QRS prolongation as in wild-type mice

muscle

cardiomyopathy ( J:237859 )

• aged mice develop mild arrhythmogenic cardiomyopathy

• 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