Analysis Tools
cardiovascular system
|
• 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
|
|
• 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
|
• 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
|
|
• 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
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| dilated cardiomyopathy 1E | DOID:0110433 |
OMIM:601154 |
J:229825 | |
| familial atrial fibrillation | DOID:0050650 |
OMIM:607554 OMIM:608583 OMIM:608988 OMIM:611493 OMIM:611494 OMIM:612201 OMIM:612240 OMIM:613055 OMIM:613980 OMIM:614022 OMIM:614049 OMIM:614050 OMIM:615377 OMIM:615378 OMIM:615770 OMIM:PS608583 |
J:229825 | |
