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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(Myh6-rtTA)8585Jam
transgene insertion 8585, John A McDonald
MGI:3712947
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cx1
Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-Fgfr3*R248C/Fgfr1)#Dor/0
involves: 129 * C57BL/6 * FVB/N * FVB/NTac MGI:5604242
cx2
Tg(Myh6-rtTA)8585Jam/0
Tg(Myh6*/tetO-SCN5A*F1759A)#Marx/0
involves: C57BL/6 * CBA * FVB/NTac MGI:5800485
cx3
Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-CUGBP1)3413Coop/0
involves: FVB * FVB/N * FVB/NTac MGI:4438035
cx4
Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-Ppargc1a)1Dpk/0
involves: FVB/N * FVB/NTac MGI:4429501


Genotype
MGI:5604242
cx1
Allelic
Composition
Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-Fgfr3*R248C/Fgfr1)#Dor/0
Genetic
Background
involves: 129 * C57BL/6 * FVB/N * FVB/NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• progressively increasing myocyte size with DOX treatment
• cardiomyocyte cross-sectional area is increased by one week of DOX treatment and continues to increase through 6 months of DOX induction
• cardiomyocyte cross-sectional area is reduced by 24% after DOX removal but remains larger than controls
• patchy areas of myocyte disarray are seen after 42 days of DOX treatment
• following 42 days of DOX treatment, hearts are larger and this increase is even more apparent after 300 days of DOX treatment
• mice show progressive development of cardiac concentric hypertrophy with preservation of systolic function from baseline through 6 months of DOX induction
• mice exhibit an elevation of left ventricle mass index by one week of DOX induction
• after 10 months of DOX treatment, concentric hypertrophy is still present, without any progression to left ventricle dilatation
• both treatment with losartan and propranolol one week prior to the start of DOX and continued throughout one week of induction abrogate the hypertrophic response (left ventricle mass index) and moderately block the increase in left ventricle posterior wall thickness
• dynamic obstruction in the proximal left ventricle is seen with six weeks of DOX treatment
• mice exhibit an increase in left ventricle diastolic posterior wall thickness within one day of DOX induction; the wall thickness is concentric and symmetrical
• left ventricle diastolic posterior wall thickness is reduced by 16% after DOX removal, but remains elevated
• increase in interstitial fibrosis is seen after 42 days of DOX treatment
• end systolic volume and end diastolic volume are decreased within one day of DOX induction
• slope of the end systolic pressure-volume relationship is elevated within 24 hours of DOX induction
• ventricular myocytes treated with DOX for 1-2 days have shorter lengths at both diastole and systole, with an overall increase in fractional shortening, indicating impaired relaxation and enhanced contraction of cardiomyocytes
• in the absence of doxycycline (DOX), mice show a small, but significant, increase in left ventricle peak outflow velocity, however cardiac mass, myocyte size and left ventricle wall thickness are normal, indicating increased contractility but no hypertrophy at baseline
• mice show an increase in contractility following DOX treatment, as evidenced by an elevated slope of the end-systolic pressure-volume relationship between the baseline and increased afterload pressure-volume following constriction of the transverse aorta
• mice treated with DOX for six weeks show elevated late-peaking outflow velocities compared to non-DOX treated mice
• left ventricle peak outflow velocity measured at the point of flow convergence in the mid-ventricle decreases by 20% after DOX removal but remains elevated compared to controls
• treatment with propranolol one week prior to the start of DOX and continued throughout one week of induction reduces the dynamic obstruction as measured by left ventricle outflow velocity but not completely
• left ventricle internal diastolic diameter is decreased within one week of DOX induction
• left ventricle mass index and left ventricle internal diastolic diameter returns to near control levels after DOX removal
• treatment with DOX leads to hypertrophic cardiomyopathy

muscle
• progressively increasing myocyte size with DOX treatment
• cardiomyocyte cross-sectional area is increased by one week of DOX treatment and continues to increase through 6 months of DOX induction
• cardiomyocyte cross-sectional area is reduced by 24% after DOX removal but remains larger than controls
• in the absence of doxycycline (DOX), mice show a small, but significant, increase in left ventricle peak outflow velocity, however cardiac mass, myocyte size and left ventricle wall thickness are normal, indicating increased contractility but no hypertrophy at baseline
• mice show an increase in contractility following DOX treatment, as evidenced by an elevated slope of the end-systolic pressure-volume relationship between the baseline and increased afterload pressure-volume following constriction of the transverse aorta
• mice treated with DOX for six weeks show elevated late-peaking outflow velocities compared to non-DOX treated mice
• left ventricle peak outflow velocity measured at the point of flow convergence in the mid-ventricle decreases by 20% after DOX removal but remains elevated compared to controls
• treatment with propranolol one week prior to the start of DOX and continued throughout one week of induction reduces the dynamic obstruction as measured by left ventricle outflow velocity but not completely
• left ventricle internal diastolic diameter is decreased within one week of DOX induction
• left ventricle mass index and left ventricle internal diastolic diameter returns to near control levels after DOX removal
• treatment with DOX leads to hypertrophic cardiomyopathy

behavior/neurological
N
• mice fed DOX for 6 months show normal exercise tolerance




Genotype
MGI:5800485
cx2
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)
No mouse lines available in IMSR.
See publication links below for author information.
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
• 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
• 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 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




Genotype
MGI:4438035
cx3
Allelic
Composition
Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-CUGBP1)3413Coop/0
Genetic
Background
involves: FVB * FVB/N * FVB/NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• following doxycycline treatment

cardiovascular system
• following doxycycline treatment for 8 days
• following doxycycline treatment
• following doxycycline treatment
• following doxycycline treatment, mice exhibit decreased posterior wall thickness during systole unlike in doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
• 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
• 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
• following doxycycline treatment for 7 to 8 days, mice exhibit reduced ejection fraction compared with doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
• following doxycycline treatment
• following doxycycline treatment, QRS complex is prolonged compared to in doxycycline-treated Tg(Myh6-rtTA)8585Jam mice

behavior/neurological
• 7 days after doxycycline treatment

muscle
• 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
• following doxycycline treatment for 7 to 8 days, mice exhibit reduced ejection fraction compared with doxycycline-treated Tg(Myh6-rtTA)8585Jam mice
• following doxycycline treatment for 8 days

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




Genotype
MGI:4429501
cx4
Allelic
Composition
Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-Ppargc1a)1Dpk/0
Genetic
Background
involves: FVB/N * FVB/NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-rtTA)8585Jam mutation (0 available)
Tg(tetO-Ppargc1a)1Dpk mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• 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
• following doxycycline treatment, adult mice exhibit eccentric hypertrophy unlike in wild-type mice
• 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
• following doxycycline treatment of adult mice
• following doxycycline treatment of adult mice
• following doxycycline treatment, adult mice exhibit decreased fractional shortening compared with wild-type mice
• however, removal of doxycycline restores cardiac muscle contractility
• following doxycycline treatment of adult mice
• following removal of doxycycline
• 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
• following doxycycline treatment, adult mice exhibit an increase in mitochondrial number along with mitochondrial ultrastructural abnormalities unlike in wild-type mice
• 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
• 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
• following doxycycline treatment, adult mice exhibit decreased fractional shortening compared with wild-type mice
• however, removal of doxycycline restores cardiac muscle contractility
• following induction of expression with doxycycline, adult mice exhibit reversible cardiomyopathy unlike wild-type mice
• however, no increase in cardiac cell apoptosis is observed





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last database update
11/22/2016
MGI 6.06
The Jackson Laboratory