Mouse Genome Informatics
cx1
     Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-CUGBP1)3413Coop/0
involves: FVB * FVB/N * FVB/NTac
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
prenatal lethality ( J:157646 )
• following doxycycline treatment

cardiovascular system
myocardial necrosis ( J:157646 )
• following doxycycline treatment for 8 days
enlarged heart ( J:157646 )
• following doxycycline treatment
increased heart weight ( J:157646 )
• following doxycycline treatment
abnormal heart left ventricle morphology ( J:157646 )
• following doxycycline treatment, mice exhibit decreased posterior wall thickness during systole unlike in doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
dilated heart left ventricle ( J:157646 )
• following doxycycline treatment, mice exhibit increased left ventricular dilation with left ventricular internal diameter in diastole and systole compared with doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
dilated cardiomyopathy ( J:157646 )
• following doxycycline treatment for 8 days, mice exhibit dilated cardiomyopathy with widespread degeneration, necrosis, and loss of myocardial fibers unlike doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
decreased cardiac muscle contractility ( J:157646 )
• following doxycycline treatment for 7 to 8 days, mice exhibit reduced ejection fraction compared with doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
prolonged PR interval ( J:157646 )
• following doxycycline treatment
prolonged QRS complex duration ( J:157646 )
• following doxycycline treatment, QRS complex is prolonged compared to in doxycycline-treated Tg(Myh6-rtTA)8585Jam mice

behavior/neurological
lethargy ( J:157646 )
• 7 days after doxycycline treatment

muscle
dilated cardiomyopathy ( J:157646 )
• following doxycycline treatment for 8 days, mice exhibit dilated cardiomyopathy with widespread degeneration, necrosis, and loss of myocardial fibers unlike doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
decreased cardiac muscle contractility ( J:157646 )
• following doxycycline treatment for 7 to 8 days, mice exhibit reduced ejection fraction compared with doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
cardiac muscle degeneration ( J:157646 )
• following doxycycline treatment for 8 days

Mouse Models of Human Disease
 OMIM IDRef(s)
Myotonic Dystrophy 1; DM1 160900 J:157646


Mouse Genome Informatics
cx2
     Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-Ppargc1a)1Dpk/0
involves: FVB * FVB/NTac
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
cardiovascular system
abnormal myocardial fiber morphology ( J:96614 )
• following doxycycline treatment of neonates, myofibril mitochondria density is increased 3.5-fold compared with wild-type myofibrils due to increased biogenesis
• doxycycline-treated adult mice exhibit an increased in mitochondrial biogenesis in myofibrils compared with wild-type mice but not to the extent observed in doxycycline treated neonates
• however, removal of doxycycline restores normal mitochondria
cardiac hypertrophy ( J:96614 )
• following doxycycline treatment, adult mice exhibit eccentric hypertrophy unlike in wild-type mice
abnormal heart left ventricle morphology ( J:96614 )
• 2 week after doxycycline treatment, adult mice exhibit increased end-diastolic and end-systolic left ventricle diameter and a mild increase in left ventricular wall thickness compared with wild-type mice
dilated heart left ventricle ( J:96614 )
• following doxycycline treatment of adult mice
dilated heart right ventricle ( J:96614 )
• following doxycycline treatment of adult mice
decreased cardiac muscle contractility ( J:96614 )
• following doxycycline treatment, adult mice exhibit decreased fractional shortening compared with wild-type mice
• however, removal of doxycycline restores cardiac muscle contractility
decreased heart rate ( J:96614 )
• following doxycycline treatment of adult mice
increased heart rate ( J:96614 )
• following removal of doxycycline
cardiomyopathy ( J:96614 )
• following induction of expression with doxycycline, adult mice exhibit reversible cardiomyopathy unlike wild-type mice
• however, no increase in cardiac cell apoptosis is observed

cellular
abnormal mitochondrion morphology ( J:96614 )
• following doxycycline treatment, adult mice exhibit an increase in mitochondrial number along with mitochondrial ultrastructural abnormalities unlike in wild-type mice
increased mitochondrial proliferation ( J:96614 )
• following doxycycline treatment of neonates, myofibril mitochondria density is increased 3.5-fold compared with wild-type myofibrils due to increased biogenesis
• doxycycline-treated adult mice exhibit an increased in mitochondrial biogenesis in myofibrils compared with wild-type mice but not to the extent observed in doxycycline treated neonates
• however, removal of doxycycline restores normal mitochondria

muscle
abnormal myocardial fiber morphology ( J:96614 )
• following doxycycline treatment of neonates, myofibril mitochondria density is increased 3.5-fold compared with wild-type myofibrils due to increased biogenesis
• doxycycline-treated adult mice exhibit an increased in mitochondrial biogenesis in myofibrils compared with wild-type mice but not to the extent observed in doxycycline treated neonates
• however, removal of doxycycline restores normal mitochondria
decreased cardiac muscle contractility ( J:96614 )
• following doxycycline treatment, adult mice exhibit decreased fractional shortening compared with wild-type mice
• however, removal of doxycycline restores cardiac muscle contractility
cardiomyopathy ( J:96614 )
• following induction of expression with doxycycline, adult mice exhibit reversible cardiomyopathy unlike wild-type mice
• however, no increase in cardiac cell apoptosis is observed