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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(Myh6-tTA)6Smbf
transgene insertion 6, Section of Myocardial Biology - Fishman Lab
MGI:2665551
Summary 10 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Clcn3tm1.1Jrhm/Clcn3tm1.1Jrhm
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
Clcn3tm1.1Jrhm/Clcn3tm1.1Jrhm
Tg(Myh6-tTA)6Smbf/0
Tg(tetO-cre)3Jig/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Clcn3tm1.1Jrhm mutation (0 available); any Clcn3 mutation (98 available)
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-cre)3Jig mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• at 3 weeks off doxycline, adult mice exhibit dramatically enlarged hears relative to age-matched on doxycline control mice
• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy
• 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

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

cardiovascular system
• at 3 weeks off doxycline, adult mice exhibit dramatically enlarged hears relative to age-matched on doxycline control mice
• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy
• 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
• 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
• 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
• 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
• 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
• at 3 weeks off doxycline, adult mice display severe signs of heart failure

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




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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetORo1-lacZ)3Conk mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice weaned from doxycycline (DOX) at 8 weeks of age die within 16 weeks of DOX removal

cardiovascular system
• after 2 weeks of DOX removal, a cellular infiltrate is seen in the myocardium
• after 4 weeks of DOX removal, patchy myocyte disarray is seen in the myocardium
• decrease in ventricular wall thickness when weaned off DOX
• enlarged ventricular chamber size in mice weaned off DOX
• 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
• mice develop dilated cardiomyopathy in systole and diastole when weaned off DOX
• however, cardiac hypertrophy is not seen
• 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
• 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
• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal
• cardiac arrhythmias develop in mice that are weaned off DOX
• 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
• 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
• some mice show signs of dehydration caused by lack of fluid intake before death

muscle
• after 2 weeks of DOX removal, a cellular infiltrate is seen in the myocardium
• after 4 weeks of DOX removal, patchy myocyte disarray is seen in the myocardium
• mice develop dilated cardiomyopathy in systole and diastole when weaned off DOX
• however, cardiac hypertrophy is not seen
• 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
• 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
• rates of muscle contraction and relaxation are prolonged in mice after 8 weeks of DOX removal

respiratory system

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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-TPR/MET,-EGFP)12Tcre mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• 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
• 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
• 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
• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth
• 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
• 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
• 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
• 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
• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth
• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth
• 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

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

muscle
• 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
• 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
• 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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-HDAC5*)1Eno mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• cellular necrosis in males after DOX withdrawal

muscle
• cellular necrosis in males after DOX withdrawal

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

behavior/neurological
• after DOX withdrawal, males become extremely lethargic 2 days before death
• after DOX withdrawal, males display decreased grooming 2 days before death
• after DOX withdrawal, males become less responsive to handling 2 days before death

cardiovascular system
• 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
• cellular necrosis in males after DOX withdrawal
• expression analysis shows inhibited PGC-1alpha and metabolic enzymes after DOX withdrawal
• after DOX withdrawal, in unanesthetized males the heart rate is decreased to 230 beats per minute, compared with about 600 in normal littermates
• inflammation is seen in males after DOX withdrawal

immune system
• inflammation is seen in males after DOX withdrawal

homeostasis/metabolism
• 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
• expression analysis shows inhibited PGC-1alpha and metabolic enzymes 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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-Mir208a)#Dzw mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

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

growth/size/body
• a dramatic increase in size is seen at 4 months of age
• heart weight to body weight ratios are increased
• chambers are enlarged and ventricle walls are thickened suggesting hypertrophic growth

cardiovascular system
• cardiomyocytes are about 50% bigger than in controls
• a dramatic increase in size is seen at 4 months of age
• heart weight to body weight ratios are increased
• chambers are enlarged and ventricle walls are thickened suggesting hypertrophic growth
• left ventricle diameter is increased in diastole and systole
• a decrease in fractional shortening is detected at 3 and 7 months of age
• 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
• at 7 months of age, prolongation of the PR interval is seen indicating a first degree atrioventricular (AV) block

muscle
• cardiomyocytes are about 50% bigger than in controls
• a decrease in fractional shortening is detected at 3 and 7 months of age




Genotype
MGI:4837876
cx6
Allelic
Composition
Tg(Myh6-tTA)6Smbf/0
Tg(tetO-EDN1,-lacZ)9Mhus/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-EDN1,-lacZ)9Mhus mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• after doxycycline withdrawal

cellular
• after doxycycline withdrawal

mortality/aging
• within 8 weeks of doxycycline withdrawal more than half of mice die
• however, mice fed doxycycline exhibit normal survival
• fewer than expected mice are generated indicating fetal loss
• however, treatment with doxycycline restores normal survival

cardiovascular system
N
• after doxycycline withdrawal, mice do not exhibit bradyarrhythmias or tachyarrhythmias
• after doxycycline withdrawal
• after doxycycline withdrawal
• after doxycycline withdrawal, cardiomyocytes contain vesiculated nuclei unlike in wild-type cells
• after doxycycline withdrawal
• after doxycycline withdrawal
• after doxycycline withdrawal, left ventricular endocardial circumference is increased compared to in wild-type mice
• after doxycycline withdrawal
• mild after doxycycline withdrawal
• 5 weeks after doxycycline withdrawal
• after doxycycline withdrawal
• lengthened progressively over time after doxycycline withdrawal
• 5 weeks after doxycycline withdrawal
• after doxycycline withdrawal

behavior/neurological
• 5 weeks after doxycycline withdrawal
• 5 weeks after doxycycline withdrawal

respiratory system
• after doxycycline withdrawal
• 5 weeks after doxycycline withdrawal

liver/biliary system
• after doxycycline withdrawal

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

immune system
• 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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-DTA)1Gfi mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

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

mortality/aging
• 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
• 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
• 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
• hearts show evidence of mild to severe myocyte loss
• atrial tissue destruction is seen in some hearts
• ventricles show patchy fibrosis following Tc withdrawal
• in some hearts, prominent ventricular dilatation is observed following Tc withdrawal
• ventricles show mild patchy fibrosis to severe fibrosis following Tc withdrawal
• 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
• 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
• following tetracycline withdrawal, atrial fibrillation occurs in some mice
• 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
• some hearts display severe cell loss following tetracycline withdrawal

muscle
• hearts show evidence of mild to severe myocyte loss
• some hearts display severe cell loss following tetracycline withdrawal

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

cellular
• 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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-NOS2,-lacZ)240iMhus mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• mild following withdrawal of doxycycline

mortality/aging
• following withdrawal of doxycycline

cardiovascular system
• 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
• mild following withdrawal of doxycycline
• at 15 to 30 weeks after doxycycline withdrawal, mice with congestive heart failure exhibit increase chamber sizes compared with wild-type mice
• following withdrawal of doxycycline
• 30 days following the withdrawal of doxycycline, mice exhibit increased left ventricular end-diastolic dimension compared with wild-type mice
• following withdrawal of doxycycline
• following withdrawal of doxycycline
• at 15 to 30 weeks after doxycycline withdrawal in mice with congestive heart failure
• at 15 to 30 weeks after doxycycline withdrawal, mice with congestive heart failure exhibit depressed hemodynamics compared with wild-type mice
• infrequently after doxycycline withdrawal
• 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
• after doxycycline withdrawal, mice exhibit bifid P waves with elongation of P-wave duration unlike wild-type mice
• progressive after doxycycline withdrawal
• 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
• after doxycycline withdrawal
• after doxycycline withdrawal
• in 6 of 78 mice 15 to 30 weeks after doxycycline withdrawal
• mild following withdrawal of doxycycline

growth/size/body
• at 15 to 30 weeks after doxycycline withdrawal, mice with congestive heart failure exhibit increase chamber sizes compared with wild-type mice
• following withdrawal of doxycycline
• at 15 to 30 weeks after doxycycline withdrawal in mice with congestive heart failure

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

immune system
• mild following withdrawal of doxycycline

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

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

muscle
• 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
• mild following withdrawal of doxycycline




Genotype
MGI:2665570
cx9
Allelic
Composition
Tg(Myh6-tTA)6Smbf/0
Tg(tetO-Vegfa)1Kesh/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-Vegfa)1Kesh mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• mesenchymal transformation and cellularization of the cardiac jelly are completely blocked in about half of E10.5 embryos
• outflow tract development is impaired with cardiac jelly remaining empty by the time it is colonized with mesenchymal cells in controls
• exhibit abnormal cardiac development upon tetracycline treatment to induce early expression of Vegfa
• 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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-tTA)6Smbf mutation (4 available)
Tg(tetO-Spp1)5Gad mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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
• 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
• at 11 weeks of age, but not 6 weeks, heart left ventricle is severely dilated
• 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
• mutants exhibit systolic dysfunction at 11 weeks of age, indicated by reduced left ventricle fractional shortening
• 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
• mice that die during the 15th week, show complete atrioventricular block, with dissociation between the sinus and idioventricular escape rhythms
• at 11 weeks of age
• at 11 weeks of age, mutants show a moderately prolonged QRS interval
• 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
• hearts are infiltrated by a large number of interstitial cells; about 50% of infiltrating cells express panleukocyte CD45 marker

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

muscle
• 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
• 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





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last database update
09/27/2022
MGI 6.21
The Jackson Laboratory