Phenotypes associated with this allele

• Allele Symbol: Tg(Myh6-tTA)6Smbf
• Allele Name: transgene insertion 6, Section of Myocardial Biology - Fishman Lab
• Allele ID: MGI:2665551
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Clcn3^tm1.1Jrhm/Clcn3^tm1.1Jrhm Tg(Myh6-tTA)6Smbf/0 Tg(tetO-cre)3Jig/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:5706585
cx2	Tg(Myh6-tTA)6Smbf/0 Tg(tetORo1-lacZ)3Conk/0	FVB.Cg-Tg(Myh6-tTA)6Smbf Tg(tetORo1-lacZ)3Conk	MGI:5905901
cx3	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-TPR/MET,-EGFP)12Tcre/0	FVB.Cg-Tg(Myh6-tTA)6Smbf Tg(tetO-TPR/MET,-EGFP)12Tcre	MGI:5911349
cx4	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-HDAC5*)1Eno/0	involves: C3H * C57BL/6 * CBA	MGI:4417970
cx5	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-Mir208a)#Dzw/0	involves: C3H * C57BL/6 * CBA	MGI:4359864
cx6	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-EDN1,-lacZ)9Mhus/0	involves: C57BL/6 * CBA	MGI:4837876
cx7	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-DTA)1Gfi/0	involves: C57BL/6 * CBA	MGI:3767677
cx8	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-NOS2,-lacZ)240iMhus/0	involves: C57BL/6 * CBA	MGI:4837726
cx9	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-Vegfa)1Kesh/0	involves: C57BL/6 * CBA	MGI:2665570
cx10	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-Spp1)5Gad/0	involves: C57BL/6 * CBA	MGI:5485272

Genotype
MGI:5706585

cn1

• Allelic Composition: Clcn3^tm1.1Jrhm/Clcn3^tm1.1Jrhm; Tg(Myh6-tTA)6Smbf/0; Tg(tetO-cre)3Jig/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:222375 )

• adult mice maintained off doxycline beyond the 3 week time point show increased mortality relative to age-matched on doxycline control mice

cardiovascular system

enlarged heart ( J:222375 )

• at 3 weeks off doxycline, adult mice exhibit dramatically enlarged hears relative to age-matched on doxycline control mice

myocardium hypertrophy ( J:222375 )

• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy

increased heart weight ( J:222375 )

• at 3 weeks off doxycycline, adult mice show a significantly increased heart mass and heart mass:body weight ratio relative to age-matched on doxycline control mice

• however, body weight is not significantly altered at 3 weeks off doxycycline

dilated cardiomyopathy ( J:222375 )

• at 1.5 and 3 weeks off doxycycline, adult mice display dilated cardiomyopathy (DCM), unlike age-matched on doxycline control mice

• DCM is more pronounced at 3 weeks off doxycycline

decreased ventricle muscle contractility ( J:222375 )

• at 3 weeks off doxycline, adult mice show significantly reduced left ventricular ejection fraction (LVEF) and fractional shortening (%FS) relative to age-matched on doxycline control mice

abnormal heart echocardiography feature ( J:222375 )

• M-mode echocardiography revealed a significant increase in the chamber cavity (left ventricular internal diameter, systolic [LVIDs] and LVID, diastolic [LVIDd]), left ventricular mass (LVM) and LVM/body weight ratio, and a marked decrease in LVEF and %FS in mice off doxycycline for 1.5 and 3 weeks relative to age-matched on doxycline control mice

abnormal myocardial fiber physiology ( J:222375 )

• electrophysiological analysis of native volume-sensitive chloride channels (VSOACs) in isolated atrial and ventricular myocytes 3 weeks off doxycycline revealed a complete elimination of hypotonic-induced VSOAC currents, whereas at 1.5 weeks, VSOAC current densities are significantly reduced, relative to age-matched on doxycycline controls; no difference in current densities are noted under isotonic conditions prior to cell swelling

• membrane capacitance is significantly increased in ventricular myocytes from mice 3 weeks off doxyclycline relative to ventricular myocytes from on doxycycline control mice; however, no difference in membrane capacitance is noted in atrial myocytes at 3 weeks off doxycycline

• at 1.5 weeks off doxycycline, residual hypotonic-induced VSOAC currents are totally abolished in isolated atrial myocytes by perfusion of 100 nM PDBu (a protein kinase C activator), similar to VSOAC currents in atrial cells from on doxycycline control mice

congestive heart failure ( J:222375 )

• at 3 weeks off doxycline, adult mice display severe signs of heart failure

muscle

myocardium hypertrophy ( J:222375 )

• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy

dilated cardiomyopathy ( J:222375 )

• at 1.5 and 3 weeks off doxycycline, adult mice display dilated cardiomyopathy (DCM), unlike age-matched on doxycline control mice

• DCM is more pronounced at 3 weeks off doxycycline

decreased ventricle muscle contractility ( J:222375 )

• at 3 weeks off doxycline, adult mice show significantly reduced left ventricular ejection fraction (LVEF) and fractional shortening (%FS) relative to age-matched on doxycline control mice

growth/size/body

enlarged heart ( J:222375 )

• at 3 weeks off doxycline, adult mice exhibit dramatically enlarged hears relative to age-matched on doxycline control mice

myocardium hypertrophy ( J:222375 )

• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy

increased heart weight ( J:222375 )

• at 3 weeks off doxycycline, adult mice show a significantly increased heart mass and heart mass:body weight ratio relative to age-matched on doxycline control mice

• however, body weight is not significantly altered at 3 weeks off doxycycline

Genotype
MGI:5905901

cx2

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetORo1-lacZ)3Conk/0
• Genetic Background: FVB.Cg-Tg(Myh6-tTA)6Smbf Tg(tetORo1-lacZ)3Conk

mortality/aging

premature death ( J:107363 )

• mice weaned from doxycycline (DOX) at 8 weeks of age die within 16 weeks of DOX removal

cardiovascular system

abnormal myocardium layer morphology ( J:107363 )

• after 2 weeks of DOX removal, a cellular infiltrate is seen in the myocardium

myocardial fiber disarray ( J:107363 )

• after 4 weeks of DOX removal, patchy myocyte disarray is seen in the myocardium

increased heart ventricle size ( J:107363 )

• enlarged ventricular chamber size in mice weaned off DOX

thin ventricular wall ( J:107363 )

• decrease in ventricular wall thickness when weaned off DOX

cardiac fibrosis ( J:107363 )

• collagen deposition is seen in the myocardium after 4 weeks of DOX removal and maximal replacement of the myocardium with collagen is seen after 8 weeks of DOX removal

dilated cardiomyopathy ( J:107363 )

• mice develop dilated cardiomyopathy in systole and diastole when weaned off DOX

• however, cardiac hypertrophy is not seen

decreased cardiac muscle contractility ( J:107363 )

• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

• the end-systolic diameter is 50% greater and aortic peak flow velocity and left ventricle fractional shortening are 40% lower than in controls in mice after 8 weeks of DOX removal

decreased ventricle muscle contractility ( J:107363 )

• after 8 weeks of DOX removal, absolute force of right ventricular papillary muscle is 50% lower than in controls

• mice show impaired left ventricular fractional shortening and aortic peak flow velocity in mice after 8 weeks of DOX removal

abnormal cardiac muscle relaxation ( J:107363 )

• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

irregular heartbeat ( J:107363 )

• cardiac arrhythmias develop in mice that are weaned off DOX

prolonged QRS complex duration ( J:107363 )

• mice weaned off DOX exhibit wide QRS complexes on the days before death indicating ventricular conduction delay

• treatment with PTX results in a 90% reduction in the number of prolonged QRS events

growth/size/body

cachexia ( J:107363 )

• 8 of 14 mice develop clinical distress just before death, with labored breathing, rough hair coat, complete inactivity, failure to eat or drink, and fluid retention

homeostasis/metabolism

dehydration ( J:107363 )

• some mice show signs of dehydration caused by lack of fluid intake before death

edema ( J:107363 )

ascites ( J:107363 )

pleural effusion ( J:107363 )

muscle

abnormal myocardium layer morphology ( J:107363 )

• after 2 weeks of DOX removal, a cellular infiltrate is seen in the myocardium

myocardial fiber disarray ( J:107363 )

• after 4 weeks of DOX removal, patchy myocyte disarray is seen in the myocardium

dilated cardiomyopathy ( J:107363 )

• mice develop dilated cardiomyopathy in systole and diastole when weaned off DOX

• however, cardiac hypertrophy is not seen

decreased cardiac muscle contractility ( J:107363 )

• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

• the end-systolic diameter is 50% greater and aortic peak flow velocity and left ventricle fractional shortening are 40% lower than in controls in mice after 8 weeks of DOX removal

decreased ventricle muscle contractility ( J:107363 )

• after 8 weeks of DOX removal, absolute force of right ventricular papillary muscle is 50% lower than in controls

• mice show impaired left ventricular fractional shortening and aortic peak flow velocity in mice after 8 weeks of DOX removal

abnormal cardiac muscle relaxation ( J:107363 )

• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

respiratory system

pleural effusion ( J:107363 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:107363

Genotype
MGI:5911349

cx3

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-TPR/MET,-EGFP)12Tcre/0
• Genetic Background: FVB.Cg-Tg(Myh6-tTA)6Smbf Tg(tetO-TPR/MET,-EGFP)12Tcre

mortality/aging

premature death ( J:241276 )

• mice die at around 4 weeks after birth (between P25 and P27) when doxycycline (DOX) is removed the day following birth to allow activation of MET in postnatal cardiomyocytes

cardiovascular system

pulmonary vascular congestion ( J:241276 )

cardiac hypertrophy ( J:241276 )

• mice show a massive progressive increase in cardiac hypertrophy from P21 to P27 when DOX is removed the day after birth

• hypertrophy is concentric as indicated by increase in the thickness/radius ratio, left ventricle mass, and left mass normalized to body weight

• treating mice with DOX at P21 rescues the cardiac hypertrophy phenotype

abnormal heart echocardiography feature ( J:241276 )

• echocardiography shows reduced left ventricle volumes, in both diastole and systole, in mice when DOX is removed a day after birth

• however, mice do not show systolic dysfunction as assessed by ejection fraction at P27

congestive heart failure ( J:241276 )

• mice die with signs of congestive heart failure including lung edema, alopecia, ascites, dyspnea, cyanosis, and lethargy following the removal of DOX the day after birth

• however, ejection fraction is preserved

behavior/neurological

lethargy ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

decreased food intake ( J:241276 )

• food intake is normal at P22 but decreases starting from P23 in mice in which DOX was removed the day after birth

growth/size/body

cardiac hypertrophy ( J:241276 )

• mice show a massive progressive increase in cardiac hypertrophy from P21 to P27 when DOX is removed the day after birth

• hypertrophy is concentric as indicated by increase in the thickness/radius ratio, left ventricle mass, and left mass normalized to body weight

• treating mice with DOX at P21 rescues the cardiac hypertrophy phenotype

decreased body weight ( J:241276 )

• greater than 27% decrease in body weight at P27 in mice when DOX is removed the day after birth

• decrease in body weight results from a reduction in body weight gain starting from P20

cachexia ( J:241276 )

• mice in which DOX was removed the day after birth develop a cardiac cachexia syndrome characterized by weight loss and reduced weight gain, decreased food intake, and skeletal muscle wasting

homeostasis/metabolism

cyanosis ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

pulmonary edema ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

• mice treated with DOX at P21 show rescue of lung edema

ascites ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

integument

alopecia ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

muscle

decreased skeletal muscle weight ( J:241276 )

• mice showing signs of congestive heart failure show wasted hindlimb muscles and have reduced skeletal muscle weight

• treating mice with DOX at P21 rescues the loss of muscular weight

respiratory system

pulmonary vascular congestion ( J:241276 )

pulmonary edema ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

• mice treated with DOX at P21 show rescue of lung edema

respiratory distress ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congestive heart failure		DOID:6000		J:241276

Genotype
MGI:4417970

cx4

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-HDAC5*)1Eno/0
• Genetic Background: involves: C3H * C57BL/6 * CBA

mortality/aging

premature death ( J:81967 )

• DOX removal results in male death within 7-10 days and within about 30 days for female

behavior/neurological

lethargy ( J:81967 )

• after DOX withdrawal, males become extremely lethargic 2 days before death

decreased grooming behavior ( J:81967 )

• after DOX withdrawal, males display decreased grooming 2 days before death

hyporesponsive to tactile stimuli ( J:81967 )

• after DOX withdrawal, males become less responsive to handling 2 days before death

cardiovascular system

abnormal heart morphology ( J:81967 )

• cristae are highly disturbed with large areas of blebbing in male mice 8 days after DOX withdrawal

• mitochondria appear swollen and 60% larger in male mice 8 days after DOX withdrawal

• the lipid body increase is reversed by 8 days after DOX withdrawal

• dramatic increase in lipid bodies in heart tissue of male mice 5 days after DOX withdrawal

myocardium necrosis ( J:81967 )

• cellular necrosis in males after DOX withdrawal

abnormal cardiovascular system physiology ( J:81967 )

• expression analysis shows inhibited PGC-1alpha and metabolic enzymes after DOX withdrawal

decreased heart rate ( J:81967 )

• after DOX withdrawal, in unanesthetized males the heart rate is decreased to 230 beats per minute, compared with about 600 in normal littermates

myocarditis ( J:81967 )

• inflammation is seen in males after DOX withdrawal

immune system

myocarditis ( J:81967 )

• inflammation is seen in males after DOX withdrawal

homeostasis/metabolism

abnormal lipid level ( J:81967 )

• dramatic increase in lipid bodies in heart tissue of male mice 5 days after DOX withdrawal

• the lipid body increase is reversed by 8 days after DOX withdrawal

abnormal metabolism ( J:81967 )

• expression analysis shows inhibited PGC-1alpha and metabolic enzymes after DOX withdrawal

muscle

myocardium necrosis ( J:81967 )

• cellular necrosis in males after DOX withdrawal

cellular

myocardium necrosis ( J:81967 )

• cellular necrosis in males after DOX withdrawal

Genotype
MGI:4359864

cx5

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-Mir208a)#Dzw/0
• Genetic Background: involves: C3H * C57BL/6 * CBA

Enlarged heart in Tg(tetO-Mir208a)#Dzw/0 Tg(Myh6-tTA)6Smbf/0 mice

cardiovascular system

abnormal myocardial fiber morphology ( J:152696 )

• cardiomyocytes are about 50% bigger than in controls

enlarged heart ( J:152696 )

• a dramatic increase in size is seen at 4 months of age

increased heart weight ( J:152696 )

• heart weight to body weight ratios are increased

cardiac hypertrophy ( J:152696 )

• chambers are enlarged and ventricle walls are thickened suggesting hypertrophic growth

abnormal heart left ventricle morphology ( J:152696 )

• left ventricle diameter is increased in diastole and systole

thick ventricular wall ( J:152696 )

cardiac interstitial fibrosis ( J:152696 )

decreased cardiac muscle contractility ( J:152696 )

• a decrease in fractional shortening is detected at 3 and 7 months of age

atrioventricular block ( J:152696 )

• about 30% of mice show second degree AV blocks, in which one or more of the electrical impulses from the atria failed to pass through the AV node to the ventricles

prolonged PR interval ( J:152696 )

• at 7 months of age, prolongation of the PR interval is seen indicating a first degree atrioventricular (AV) block

muscle

abnormal myocardial fiber morphology ( J:152696 )

• cardiomyocytes are about 50% bigger than in controls

decreased cardiac muscle contractility ( J:152696 )

• a decrease in fractional shortening is detected at 3 and 7 months of age

growth/size/body

enlarged heart ( J:152696 )

• a dramatic increase in size is seen at 4 months of age

increased heart weight ( J:152696 )

• heart weight to body weight ratios are increased

cardiac hypertrophy ( J:152696 )

• chambers are enlarged and ventricle walls are thickened suggesting hypertrophic growth

cellular

cardiac interstitial fibrosis ( J:152696 )

Genotype
MGI:4837876

cx6

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-EDN1,-lacZ)9Mhus/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:131245 )

• within 8 weeks of doxycycline withdrawal more than half of mice die

• however, mice fed doxycycline exhibit normal survival

prenatal lethality, incomplete penetrance ( J:131245 )

• fewer than expected mice are generated indicating fetal loss

• however, treatment with doxycycline restores normal survival

cardiovascular system

cardiovascular system phenotype ( J:131245 )

N • after doxycycline withdrawal, mice do not exhibit bradyarrhythmias or tachyarrhythmias

liver vascular congestion ( J:131245 )

• after doxycycline withdrawal

pulmonary vascular congestion ( J:131245 )

• after doxycycline withdrawal

abnormal myocardial fiber morphology ( J:131245 )

• after doxycycline withdrawal, cardiomyocytes contain vesiculated nuclei unlike in wild-type cells

increased myocardial fiber size ( J:131245 )

• after doxycycline withdrawal

cardiac muscle necrosis ( J:131245 )

• after doxycycline withdrawal

abnormal ventricle endocardium morphology ( J:131245 )

• after doxycycline withdrawal, left ventricular endocardial circumference is increased compared to in wild-type mice

increased heart weight ( J:131245 )

• after doxycycline withdrawal

cardiac fibrosis ( J:131245 )

• mild after doxycycline withdrawal

decreased left ventricle systolic pressure ( J:131245 )

• 5 weeks after doxycycline withdrawal

prolonged P wave ( J:131245 )

• after doxycycline withdrawal

prolonged QRS complex duration ( J:131245 )

• lengthened progressively over time after doxycycline withdrawal

decreased systemic arterial systolic blood pressure ( J:131245 )

• 5 weeks after doxycycline withdrawal

heart inflammation ( J:131245 )

• after doxycycline withdrawal

behavior/neurological

hunched posture ( J:131245 )

• 5 weeks after doxycycline withdrawal

decreased locomotor activity ( J:131245 )

• 5 weeks after doxycycline withdrawal

respiratory system

pulmonary vascular congestion ( J:131245 )

• after doxycycline withdrawal

respiratory distress ( J:131245 )

• 5 weeks after doxycycline withdrawal

liver/biliary system

liver vascular congestion ( J:131245 )

• after doxycycline withdrawal

muscle

abnormal myocardial fiber morphology ( J:131245 )

• after doxycycline withdrawal, cardiomyocytes contain vesiculated nuclei unlike in wild-type cells

increased myocardial fiber size ( J:131245 )

• after doxycycline withdrawal

cardiac muscle necrosis ( J:131245 )

• after doxycycline withdrawal

immune system

heart inflammation ( J:131245 )

• after doxycycline withdrawal

growth/size/body

increased heart weight ( J:131245 )

• after doxycycline withdrawal

cellular

cardiac muscle necrosis ( J:131245 )

• after doxycycline withdrawal

Genotype
MGI:3767677

cx7

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-DTA)1Gfi/0
• Genetic Background: involves: C57BL/6 * CBA

Cardiac fibrosis and ventricle dilatation in Tg(Myh6-tTA)6Smbf/0 Tg(tetO-DTA)1Gfi/0 mice

mortality/aging

premature death ( J:128617 )

• when Tc treatment is withdrawn after birth, mortality results with median survival time of 37 days (earliest time of death is 12 days after withdrawal of Tc, latest death is 77 days); death occurs suddenly with no indication of illness

lethality throughout fetal growth and development, complete penetrance ( J:128617 )

• in absence of maternal supplementation with tetracycline (Tc) during gestation, no binary (or double) transgenic offspring are born, whereas gestational or perinatal suppressive Tc treatment results in Mendelian numbers of binary offspring (22%)

• genotypic analysis at times throughout gestation show that death of double transgenic embryos occurs between 10.5 days post conception (dpc) and fetal day 19

embryonic lethality during organogenesis, incomplete penetrance ( J:128617 )

• in absence of maternal supplementation with tetracycline (Tc) during gestation, no binary (or double) transgenic offspring are born, whereas gestational or perinatal suppressive Tc treatment results in Mendelian numbers of binary offspring (22%)

• genotypic analysis at times throughout gestation show that death of double transgenic embryos occurs between 10.5 days post conception (dpc) and fetal day 19

cardiovascular system

decreased myocardial fiber number ( J:128617 )

• hearts show evidence of mild to severe myocyte loss

abnormal heart atrium morphology ( J:128617 )

• atrial tissue destruction is seen in some hearts

abnormal heart ventricle morphology ( J:128617 )

• ventricles show patchy fibrosis following Tc withdrawal

dilated heart ventricle ( J:128617 )

• in some hearts, prominent ventricular dilatation is observed following Tc withdrawal

cardiac fibrosis ( J:128617 )

• ventricles show mild patchy fibrosis to severe fibrosis following Tc withdrawal

ventricular tachycardia ( J:128617 )

• at 1 month after Tc withdrawal, most isolated-perfused hearts display either spontaneous or inducible ventricular tachycardia, including both sustained and nonsustained runs of ventricular tachycardia with some episodes lasting

irregular heartbeat ( J:128617 )

• following Tc withdrawal, a variety of arrhythmias are detected in double transgenic mice which show increased propensity to develop reentrant tachycardia, including atrial fibrillation, pauses, and complex ventricular ectopy such as runs of ventricular tachycardia

• majority of even mildly diseased hearts are arrhythmogenic

atrial fibrillation ( J:128617 )

• following tetracycline withdrawal, atrial fibrillation occurs in some mice

abnormal impulse conducting system conduction ( J:128617 )

• at 1 month after tetracycline withdrawal, a subset of isolated-perfused hearts display markedly disturbed activation profiles, with either disorganized conduction or evidence of block during pacing

• majority of even mildly diseased hearts are arrhythmogenic

increased cardiomyocyte apoptosis ( J:128617 )

• some hearts display severe cell loss following tetracycline withdrawal

muscle

decreased myocardial fiber number ( J:128617 )

• hearts show evidence of mild to severe myocyte loss

increased cardiomyocyte apoptosis ( J:128617 )

• some hearts display severe cell loss following tetracycline withdrawal

homeostasis/metabolism

abnormal atrial thrombosis ( J:128617 )

• mural thrombus formation is prominent in atrial tissue in some animals following Tc withdrawal

cellular

increased cardiomyocyte apoptosis ( J:128617 )

• some hearts display severe cell loss following tetracycline withdrawal

Genotype
MGI:4837726

cx8

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-NOS2,-lacZ)240iMhus/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:132082 )

• following withdrawal of doxycycline

cardiovascular system

abnormal atrioventricular node morphology ( J:132082 )

• after doxycycline withdrawal, mice exhibit a trend towards increased inflammation in the atrioventricular node unlike wild-type mice

• however, there is no evidence of fibrosis, calcification, or necrosis

cardiac muscle necrosis ( J:132082 )

• mild following withdrawal of doxycycline

enlarged heart ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal, mice with congestive heart failure exhibit increase chamber sizes compared with wild-type mice

increased heart weight ( J:132082 )

• following withdrawal of doxycycline

abnormal heart left ventricle morphology ( J:132082 )

• 30 days following the withdrawal of doxycycline, mice exhibit increased left ventricular end-diastolic dimension compared with wild-type mice

increased heart ventricle size ( J:132082 )

• following withdrawal of doxycycline

dilated heart ventricle ( J:132082 )

• following withdrawal of doxycycline

cardiac interstitial fibrosis ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal in mice with congestive heart failure

abnormal cardiovascular system physiology ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal, mice with congestive heart failure exhibit depressed hemodynamics compared with wild-type mice

ventricular tachycardia ( J:132082 )

• infrequently after doxycycline withdrawal

absent heartbeat ( J:132082 )

• after doxycycline withdrawal, mice exhibit sudden cardiac death associated with cardiac asystole preceded by a short burst of 2:1 block unlike wild-type mice

abnormal P wave ( J:132082 )

• after doxycycline withdrawal, mice exhibit bifid P waves with elongation of P-wave duration unlike wild-type mice

heart block ( J:132082 )

• progressive after doxycycline withdrawal

atrioventricular block ( J:132082 )

• after doxycycline withdrawal, 4 mice exhibit atrioventricular block with Wenckebach periodicity (i.e. progressive elongation of PR interval followed by dropped ventricular beats) unlike wild-type mice

prolonged PR interval ( J:132082 )

• after doxycycline withdrawal

prolonged P wave ( J:132082 )

• after doxycycline withdrawal

congestive heart failure ( J:132082 )

• in 6 of 78 mice 15 to 30 weeks after doxycycline withdrawal

heart inflammation ( J:132082 )

• mild following withdrawal of doxycycline

growth/size/body

enlarged heart ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal, mice with congestive heart failure exhibit increase chamber sizes compared with wild-type mice

increased heart weight ( J:132082 )

• following withdrawal of doxycycline

increased body weight ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal in mice with congestive heart failure

homeostasis/metabolism

edema ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal in mice with congestive heart failure

immune system

heart inflammation ( J:132082 )

• mild following withdrawal of doxycycline

behavior/neurological

lethargy ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal in mice with congestive heart failure

respiratory system

respiratory distress ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal in mice with congestive heart failure

muscle

abnormal atrioventricular node morphology ( J:132082 )

• after doxycycline withdrawal, mice exhibit a trend towards increased inflammation in the atrioventricular node unlike wild-type mice

• however, there is no evidence of fibrosis, calcification, or necrosis

cardiac muscle necrosis ( J:132082 )

• mild following withdrawal of doxycycline

cellular

cardiac muscle necrosis ( J:132082 )

• mild following withdrawal of doxycycline

cardiac interstitial fibrosis ( J:132082 )

• at 15 to 30 weeks after doxycycline withdrawal in mice with congestive heart failure

Genotype
MGI:2665570

cx9

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-Vegfa)1Kesh/0
• Genetic Background: involves: C57BL/6 * CBA

cardiovascular system

abnormal cardiac epithelial to mesenchymal transition ( J:68214 )

• mesenchymal transformation and cellularization of the cardiac jelly are completely blocked in about half of E10.5 embryos

abnormal cardiac outflow tract development ( J:68214 )

• outflow tract development is impaired with cardiac jelly remaining empty by the time it is colonized with mesenchymal cells in controls

abnormal heart development ( J:68214 )

• exhibit abnormal cardiac development upon tetracycline treatment to induce early expression of Vegfa

abnormal endocardium morphology ( J:68214 )

• multi-layered endocardium

Genotype
MGI:5485272

cx10

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-Spp1)5Gad/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:194810 )

• mutants show a large increase in mortality occurring between the 8th and 15th week after birth, with a half-life of 12 weeks

cardiovascular system

abnormal heart morphology ( J:194810 )

• cellular organization in hearts is altered after 11 weeks of age, with evidence of myocyte loss and interstitial cell infiltratio

• the number of apoptotic cells in the hear is increased at 11 weeks of age

dilated heart left ventricle ( J:194810 )

• at 11 weeks of age, but not 6 weeks, heart left ventricle is severely dilated

dilated cardiomyopathy ( J:194810 )

• at 11 weeks of age, the left ventricle free wall is thinner during systole than in controls, suggesting the development of a hypokinetic dilated cardiomyopathy

decreased cardiac muscle contractility ( J:194810 )

• mutants exhibit systolic dysfunction at 11 weeks of age, indicated by reduced left ventricle fractional shortening

abnormal impulse conducting system conduction ( J:194810 )

• ECG intervals during the last ECG recording before death show differences in PQ, QRS, QT, and QTc but not of RR

• mice that survive exhibit ECG parameters with normal values, with a moderate prolongation of PQ and QRS intervals

atrioventricular block ( J:194810 )

• mice that die during the 15th week, show complete atrioventricular block, with dissociation between the sinus and idioventricular escape rhythms

prolonged PQ interval ( J:194810 )

• at 11 weeks of age

prolonged QRS complex duration ( J:194810 )

• at 11 weeks of age, mutants show a moderately prolonged QRS interval

abnormal T wave ( J:194810 )

• at 11 weeks of age, ECGs show an abnormal repolarization with disappearance of the early positive phase of the T wave commonly seen in controls

• at 11 weeks of age, the T-wave duration is prolonged

• however, the QT interval is not prolonged

heart inflammation ( J:194810 )

• hearts are infiltrated by a large number of interstitial cells; about 50% of infiltrating cells express panleukocyte CD45 marker

myocarditis ( J:194810 )

immune system

heart inflammation ( J:194810 )

• hearts are infiltrated by a large number of interstitial cells; about 50% of infiltrating cells express panleukocyte CD45 marker

myocarditis ( J:194810 )

muscle

dilated cardiomyopathy ( J:194810 )

• at 11 weeks of age, the left ventricle free wall is thinner during systole than in controls, suggesting the development of a hypokinetic dilated cardiomyopathy

decreased cardiac muscle contractility ( J:194810 )

• mutants exhibit systolic dysfunction at 11 weeks of age, indicated by reduced left ventricle fractional shortening

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:194810