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Phenotypes Associated with This Genotype
Genotype
MGI:5800485
Allelic
Composition
Tg(Myh6-rtTA)8585Jam/0
Tg(Myh6*/tetO-SCN5A*F1759A)#Marx/0
Genetic
Background
involves: C57BL/6 * CBA * FVB/NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-rtTA)8585Jam mutation (1 available)
Tg(Myh6*/tetO-SCN5A*F1759A)#Marx mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Atrial and ventricular cardiomyopathy in Tg(Myh6*/tetO-SCN5A*F1759A)#Marx/0 Tg(Myh6-rtTA)8585Jam/0 mice

cardiovascular system
• 3-4 month old mice exhibit myocyte disarray
• by 12 weeks of age, atrial and ventricular cardiomyocytes show mitochondrial injury, with circular and swollen mitochondria and ruptured outer membranes
• atrial remodeling is seen at very early stages after birth in the absence of doxycyline
• atria progressively enlarge over several months after birth
• 3-4 month old mice exhibit atrial hypertrophy, with an increase of right and left atrial areas by 52% and 54%, respectively
• left atrial size is increased by 48% at 20-30 days of age compared to controls and persists through at least 3 months of age
• the diameter of T-tubules is increased by 2.5-fold in the ventricle at 6 and 12 weeks of age
• ventricles progressively enlarge over several months after birth
• 3-4 month old mice exhibit increased fibrosis
• the left ventricular ejection fraction is reduced nonsignificantly by 14% at 20-30 days of age, and modestly decreased by 27% and 35% at 41-50 days and 51-80 days, respectively
• increase in frequency of nonsustained polymorphic ventricular tachycardia
• spontaneous prolonged periods of atrial fibrillation are seen (in both anesthetized and nonanesthetized mice) as early as 5-6 weeks of age and by 10 weeks of age in more than 80% of mice in the absence of doxycycline
• prolonged action potential duration and rotors, as well as wave and wavelets in the atria
• treatment with a specific inhibitor of the sodium-calcium exchanger, SEA-0400, reduces the fraction of atrial fibrillation over a 20-hour period in 4 of 5 mice
• increase in frequency of premature ventricular complexes
• treatment with SEA-0400 reduces the frequency of premature ventricular complexes by 76%, without affecting the QT interval
• however, ventricular arrhythmias are not seen
• the voltage at which the sodium channel Scn5a (Nav1.5) is open 50% of the time in ventricular cardiomyocytes is shifted in a hyperpolarizing direction by 3.3 mV and inactivation is shifted in the depolarizing direction by 1.9 mV leading to enhanced window current
• greater than 5% of peak sodium current remains after exposure to 3 mM lidocaine in more than 60% of atrial and ventricular cardiomyocytes indicating increased persistent sodium current; this residual lidocaine-resistant sodium current is not seen in controls
• the persistent sodium current is resistant to ranolazine
• mice develop cardiomyopathy in the absence of doxycycline

homeostasis/metabolism
• mild myofibril disarray is seen at 6 weeks of age, with increased collagen deposition in the atria which progresses with glycogen deposition at 12 weeks of age

muscle
• 3-4 month old mice exhibit myocyte disarray
• by 12 weeks of age, atrial and ventricular cardiomyocytes show mitochondrial injury, with circular and swollen mitochondria and ruptured outer membranes
• the left ventricular ejection fraction is reduced nonsignificantly by 14% at 20-30 days of age, and modestly decreased by 27% and 35% at 41-50 days and 51-80 days, respectively
• mice develop cardiomyopathy in the absence of doxycycline
• mild myofibril disarray is seen at 6 weeks of age, with increased collagen deposition in the atria which progresses with glycogen deposition at 12 weeks of age


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
07/16/2019
MGI 6.14
The Jackson Laboratory