Phenotypes associated with this allele

• Allele Symbol: Tg(Myh6-tTA)55Rbns
• Allele Name: transgene insertion 55, Jeffrey Robbins
• Allele ID: MGI:3757936
• Summary: 22 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Pln^tm1Egk/Pln^tm1Egk Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: 129S2/SvPas * FVB	MGI:5897396
cx2	Ppp3cb^tm1Jmk/Ppp3cb^tm1Jmk Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: 129S6/SvEvTac * FVB	MGI:5897404
cx3	Atp2a2^tm1Ges/Atp2a2^+ Tg(Myh6/tetO-Tnnc1*L48Q)2Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: 129X1/SvJ * FVB	MGI:5897401
cx4	Atp2a2^tm1Ges/Atp2a2^+ Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: 129X1/SvJ * FVB	MGI:5897399
cx5	Myh6^tm1Jse/Myh6^+ Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: 129X1/SvJ * FVB	MGI:5897392
cx6	Tg(Myh6*/tetO-Hspb8*K141N)#Atsa/0 Tg(Myh6-tTA)55Rbns/0	involves: C57BL/6CrSlc * FVB/NJ	MGI:6294492
cx7	Tg(Myh6*/tetO-BAG3)69Atsa/0 Tg(Myh6-tTA)55Rbns/0	involves: C57BL/6CrSlc * FVB/NJ	MGI:6294706
cx8	Tg(Myh6-Map2k1*)1Jmol/0 Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: FVB	MGI:5897405
cx9	Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: FVB	MGI:5897383
cx10	Tg(Myh6/tetO-Tnnc1*L48Q)2Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: FVB	MGI:5897387
cx11	Tg(Myh6*/tetO-FXYD1*S68E)39Jych/0 Tg(Myh6-tTA)55Rbns/0	involves: FVB/N	MGI:5780749
cx12	Tg(Myh6/tetO-POSTN)22.1Jmol/0 Tg(Myh6-tTA)55Rbns/0	involves: FVB/N	MGI:3819379
cx13	Tg(Myh6-tTA)55Rbns/0 Tg(Myh6/tetO-PRKCA*)1Jmk/0	involves: FVB/N	MGI:3851897
cx14	Tg(Myh6-tTA)55Rbns/0 Tg(tetO-Dusp6)1Jmol/0	involves: FVB/N	MGI:3851933
cx15	Tg(Myh6-Gnaq)#Gwd/0 Tg(Myh6-tTA)55Rbns/0 Tg(tetO-Bnip3l)1Gwd/0	involves: FVB/N	MGI:4430402
cx16	Tg(Myh6-tTA)55Rbns/0 Tg(tetO-Bnip3l)1Gwd/0	involves: FVB/N	MGI:4430403
cx17	Tg(Myh6*/tetO-Slc8a1)BJych/0 Tg(Myh6-tTA)55Rbns/0	involves: FVB/N	MGI:5780592
cx18	Tg(Myh6/tetO-Mybpc3*)#Rbns/0 Tg(Myh6-tTA)55Rbns/0	involves: FVB/N	MGI:5909973
cx19	Tg(Myh6-tTA)55Rbns/0 Tg(Myh6/tetO-PRKAG2*N488I)1Chib/0	Not Specified	MGI:3841180
cx20	Tg(Myh6-tTA)55Rbns/? Tg(Myh6/tetO-BNIP3)1Gwd/?	Not Specified	MGI:3764675
cx21	Tg(Myh6-tTA)55Rbns/0 Tg(Myh6/tetO-Gsk3b*S9A)1Rbns/0	Not Specified	MGI:3757977
cx22	Tg(Myh6-tTA)55Rbns/0 Tg(Myh6*/tetO-GCaMP2)1Mik/0	Not Specified	MGI:3758000

Genotype
MGI:5897396

cx1

• Allelic Composition: Pln^tm1Egk/Pln^tm1Egk; Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: 129S2/SvPas * FVB

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

cardiovascular system

abnormal interventricular septum morphology ( J:234490 )

• improved compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

increased heart weight ( J:234490 )

• more severe than in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

increased heart left ventricle size ( J:234490 )

• as in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

abnormal myocardial fiber physiology ( J:234490 )

• faster mechanical relaxation of myocyte contraction compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol

abnormal myocardial fiber calcium currents ( J:234490 )

• faster Ca2+ transient decay time compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol

growth/size/body

increased heart weight ( J:234490 )

• more severe than in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

Genotype
MGI:5897404

cx2

• Allelic Composition: Ppp3cb^tm1Jmk/Ppp3cb^tm1Jmk; Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: 129S6/SvEvTac * FVB

cardiovascular system

thin interventricular septum ( J:234490 )

• as in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

increased heart weight ( J:234490 )

• less than in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

increased heart left ventricle size ( J:234490 )

• as in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

decreased cardiac muscle contractility ( J:234490 )

• more so than in Ppp3cb^tm1Jmk homozygotes and similar to in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

muscle

decreased cardiac muscle contractility ( J:234490 )

• more so than in Ppp3cb^tm1Jmk homozygotes and similar to in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

growth/size/body

increased heart weight ( J:234490 )

• less than in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

Genotype
MGI:5897401

cx3

• Allelic Composition: Atp2a2^tm1Ges/Atp2a2⁺; Tg(Myh6/tetO-Tnnc1*L48Q)2Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: 129X1/SvJ * FVB

cardiovascular system

thick interventricular septum ( J:234490 )

• compared to in Tg(Myh6/tetO-Tnnc1*L48Q)2Jmol mice

increased heart weight ( J:234490 )

• more so than in Tg(Myh6/tetO-Tnnc1*L48Q)2Jmol mice

abnormal heart left ventricle morphology ( J:234490 )

• increased left ventricle wall thickness compared to in Tg(Myh6/tetO-Tnnc1*L48Q)2Jmol mice

abnormal myocardial fiber physiology ( J:234490 )

• increased unloaded twitch force

growth/size/body

increased heart weight ( J:234490 )

• more so than in Tg(Myh6/tetO-Tnnc1*L48Q)2Jmol mice

Genotype
MGI:5897399

cx4

• Allelic Composition: Atp2a2^tm1Ges/Atp2a2⁺; Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: 129X1/SvJ * FVB

cardiovascular system

increased heart weight ( J:234490 )

• more so than in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

increased heart left ventricle size ( J:234490 )

• improved compared to in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

abnormal myocardial fiber physiology ( J:234490 )

• increased unloaded twitch force

growth/size/body

increased heart weight ( J:234490 )

• more so than in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

Genotype
MGI:5897392

cx5

• Allelic Composition: Myh6^tm1Jse/Myh6⁺; Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: 129X1/SvJ * FVB

mortality/aging

premature death ( J:234490 )

• improved compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

cardiovascular system

abnormal interventricular septum morphology ( J:234490 )

• improved compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

increased heart weight ( J:234490 )

• improved compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

increased heart left ventricle size ( J:234490 )

• improved compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

abnormal cardiac muscle contractility ( J:234490 )

• mice exhibit improved fractional shortening compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

muscle

abnormal cardiac muscle contractility ( J:234490 )

• mice exhibit improved fractional shortening compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

growth/size/body

increased heart weight ( J:234490 )

• improved compared with Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

Genotype
MGI:6294492

cx6

• Allelic Composition: Tg(Myh6*/tetO-Hspb8*K141N)#Atsa/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: C57BL/6CrSlc * FVB/NJ

cardiovascular system

abnormal heart morphology ( J:197853 )

• intracellular aggregates containing the mutant protein and amyloid oligomer are seen in the hearts of 6 months old mice

cardiac hypertrophy ( J:197853 )

• mice exhibit cardiac hypertrophy, with increased heart weight/body weight ratios at 6 months of age

cardiac fibrosis ( J:197853 )

• hearts exhibit mild apical cardiac fibrosis at 6 months of age

decreased cardiac muscle contractility ( J:197853 )

• fractional shortening and ejection fraction are slightly reduced in 6 month old mice, indicating slightly reduced cardiac function

cardiomyopathy ( J:197853 )

• mice develop cardiac disease by 6 months of age

cellular

abnormal oxidative phosphorylation ( J:197853 )

• oxidative phosphorylation ratio, respiratory control index, and oxygen consumption in state 3 are decreased in heart mitochondria of 6 month old mice

homeostasis/metabolism

amyloid beta deposits ( J:197853 )

• intracellular aggregates containing amyloid oligomer are seen in hearts of 6 month old mice

muscle

decreased cardiac muscle contractility ( J:197853 )

• fractional shortening and ejection fraction are slightly reduced in 6 month old mice, indicating slightly reduced cardiac function

cardiomyopathy ( J:197853 )

• mice develop cardiac disease by 6 months of age

nervous system

amyloid beta deposits ( J:197853 )

• intracellular aggregates containing amyloid oligomer are seen in hearts of 6 month old mice

growth/size/body

cardiac hypertrophy ( J:197853 )

• mice exhibit cardiac hypertrophy, with increased heart weight/body weight ratios at 6 months of age

Genotype
MGI:6294706

cx7

• Allelic Composition: Tg(Myh6*/tetO-BAG3)69Atsa/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: C57BL/6CrSlc * FVB/NJ

cardiovascular system

abnormal heart morphology ( J:273465 )

• mice exhibit an upregulation of cardiac atrial natriuretic peptide and of autophagy marker proteins Map1lc3a (LC3-II) and beclin 1, and reduced protein levels of small heat shock proteins Cryab and Hspb1

• however, heart weight/body weight is similar to controls and no inclusion bodies are seen in hearts

decreased cardiac muscle contractility ( J:273465 )

• fractional shortening is slightly decreased

cellular

abnormal autophagy ( J:273465 )

• mice exhibit upregulation of autophagy marker proteins Map1lc3a (LC3-II) and beclin 1, and reduced protein levels of small heat shock proteins Cryab and Hspb1 indicating enhanced BAG3-activated autophagy system

• mice treated with chloroquine, an inhibitor of the autophagy system, show recovery of Cryab and Hspb1 protein levels and exhibit autophagosomes and autolysosome-like structures in heart ventricles which are not seen in controls

homeostasis/metabolism

abnormal autophagy ( J:273465 )

• mice exhibit upregulation of autophagy marker proteins Map1lc3a (LC3-II) and beclin 1, and reduced protein levels of small heat shock proteins Cryab and Hspb1 indicating enhanced BAG3-activated autophagy system

• mice treated with chloroquine, an inhibitor of the autophagy system, show recovery of Cryab and Hspb1 protein levels and exhibit autophagosomes and autolysosome-like structures in heart ventricles which are not seen in controls

muscle

decreased cardiac muscle contractility ( J:273465 )

• fractional shortening is slightly decreased

Genotype
MGI:5897405

cx8

• Allelic Composition: Tg(Myh6-Map2k1*)1Jmol/0; Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: FVB

cardiovascular system

thick interventricular septum ( J:234490 )

• compared to in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol and wild-type mice

increased heart weight ( J:234490 )

• compared with wild-type mice

abnormal heart left ventricle morphology ( J:234490 )

• left ventricular wall thickness is increased compared with wild-type and Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

• however, left ventricle size is rescued compared to in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

increased cardiac muscle contractility ( J:234490 )

• compared to in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

muscle

increased cardiac muscle contractility ( J:234490 )

• compared to in Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol mice

growth/size/body

increased heart weight ( J:234490 )

• compared with wild-type mice

Genotype
MGI:5897383

cx9

• Allelic Composition: Tg(Myh6/tetO-Tnnc1*I61Q)1Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: FVB

mortality/aging

premature death ( J:234490 )

• some mice die by 4 months of age with no mice surviving beyond 8 months

cardiovascular system

thin interventricular septum ( J:234490 )

• at baseline

increased heart weight ( J:234490 )

• at baseline

increased heart left ventricle size ( J:234490 )

• at baseline

decreased cardiac muscle contractility ( J:234490 )

• at baseline

increased cardiac muscle relaxation ( J:234490 )

• at baseline

abnormal myocardial fiber physiology ( J:234490 )

• reduced time at elevated tension with a set amount of Ca+2

• increased diastolic Ca2+ concentration

muscle

decreased cardiac muscle contractility ( J:234490 )

• at baseline

increased cardiac muscle relaxation ( J:234490 )

• at baseline

abnormal sarcomere morphology ( J:234490 )

• elongated and increased length-to-width ratios at baseline

growth/size/body

increased heart weight ( J:234490 )

• at baseline

Genotype
MGI:5897387

cx10

• Allelic Composition: Tg(Myh6/tetO-Tnnc1*L48Q)2Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: FVB

cardiovascular system

cardiovascular system phenotype ( J:234490 )

N • mice exhibit normal cardiac growth and chamber dimensions up to 1 year of age

thick interventricular septum ( J:234490 )

• in mice treated with metoprolol

increased heart weight ( J:234490 )

• in mice treated with metoprolol

• following transverse aortic constriction to induce pressure overload

cardiac hypertrophy ( J:234490 )

• following transverse aortic constriction to induce pressure overload, mice exhibit increased hypertrophy compared with wild-type mice

increased heart left ventricle size ( J:234490 )

• in mice treated with metoprolol

• following transverse aortic constriction to induce pressure overload

abnormal cardiac muscle contractility ( J:234490 )

• mice treated with metoprolol exhibit no effect on systolic performance unlike wild-type mice

• following transverse aortic constriction to induce pressure overload, mice fail to exhibit an increased in fractional shortening unlike wild-type mice

increased cardiac muscle contractility ( J:234490 )

• despite smaller Ca+2 amplitudes

decreased cardiac muscle relaxation ( J:234490 )

• prolonged relaxation and rate of Ca2+ transient decay

• however, mice exhibit normal relaxation time and Ca2+ decay time whether treated with isopropynol

abnormal myocardial fiber physiology ( J:234490 )

• prolonged time at elevated tension with a set amount of Ca+2

• enhanced myofilament Ca2+ sensitivity

decreased response of heart to induced stress ( J:234490 )

• following transverse aortic constriction to induce pressure overload, mice exhibit increased hypertrophy but fail to exhibit an increased in fractional shortening unlike wild-type mice

homeostasis/metabolism

decreased response of heart to induced stress ( J:234490 )

• following transverse aortic constriction to induce pressure overload, mice exhibit increased hypertrophy but fail to exhibit an increased in fractional shortening unlike wild-type mice

decreased physiological sensitivity to xenobiotic ( J:234490 )

• mice treated with metoprolol exhibit no effect on systolic performance with increased left ventricular chamber dimension, septal wall thickness and cardiac mass compared with wild-type mice

• however, mice exhibit normal relaxation time and Ca2+ decay time whether treated with isopropynol

muscle

abnormal cardiac muscle contractility ( J:234490 )

• mice treated with metoprolol exhibit no effect on systolic performance unlike wild-type mice

• following transverse aortic constriction to induce pressure overload, mice fail to exhibit an increased in fractional shortening unlike wild-type mice

increased cardiac muscle contractility ( J:234490 )

• despite smaller Ca+2 amplitudes

decreased cardiac muscle relaxation ( J:234490 )

• prolonged relaxation and rate of Ca2+ transient decay

• however, mice exhibit normal relaxation time and Ca2+ decay time whether treated with isopropynol

growth/size/body

increased heart weight ( J:234490 )

• in mice treated with metoprolol

• following transverse aortic constriction to induce pressure overload

cardiac hypertrophy ( J:234490 )

• following transverse aortic constriction to induce pressure overload, mice exhibit increased hypertrophy compared with wild-type mice

Genotype
MGI:5780749

cx11

• Allelic Composition: Tg(Myh6*/tetO-FXYD1*S68E)39Jych/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: FVB/N

mortality/aging

premature death ( J:182365 )

• untreated mice exhibit increased mortality (8/15) starting at 4 weeks of age, however, in survivors reaching 22 weeks of age only 1 mouse out of 20 dies

• most deaths occur between 4 to 6 weeks of age

cardiovascular system

cardiac hypertrophy ( J:182365 )

increased heart left ventricle size ( J:182365 )

• increased left ventricular mass as compared to controls

decreased cardiac output ( J:182365 )

• reduced cardiac output at 4 weeks, however, by 22 weeks CO is similar to controls

increased cardiac stroke volume ( J:182365 )

abnormal cardiac muscle contractility ( J:182365 )

• mice exhibit a blunted response to beta-adrenergic agonists

• although resting +dP/dt and - dP/dt are similar to wild-type, maximal +dP/dt and -dP/dt at 18-22 weeks are reduced following isoproterenol infusion

• maximal contraction amplitude is lower than wild-type at 5 mM [Ca²⁺]

increased heart ventricle muscle contractility ( J:182365 )

• increased ejection fraction

abnormal sinus arrhythmia ( J:182365 )

decreased heart rate ( J:182365 )

• heart rate is less than 50% of controls at 4 weeks

• reduced heart rate at 18-22 weeks before and after isoproterenol (beta-adrenergic agonist) infusion

• 11/ 12 mice exhibit severe bradycardia

• bradycardia persists at 22 weeks in 6/7 survivors

ventricular tachycardia ( J:182365 )

• multifocal ventricular tachycardia

• tachycardia persists at 22 weeks in 1/7 survivors

ventricular fibrillation ( J:182365 )

• 4/ 12 mice exhibit ventricular flutter/fibrillation

abnormal myocardial fiber physiology ( J:182365 )

• I_pump is lower by 41.7% as compared to wild-type

• peak density of I_Ca is decreased by 29.2%

• Peak amplitudes of depolarization-activated K⁺ currents are lower as compared to wild-type

• diastolic intracellular Ca²⁺ is increased

• systolic intracellular Ca²⁺ is similar to wild-type at baseline, but lower after stimulation with isoproterenol

• decreased sarcoplasmic reticulum Ca²⁺ uptake

• decreased Na⁺ K⁺-ATPase activity

growth/size/body

cardiac hypertrophy ( J:182365 )

decreased body size ( J:182365 )

muscle

abnormal cardiac muscle contractility ( J:182365 )

• mice exhibit a blunted response to beta-adrenergic agonists

• although resting +dP/dt and - dP/dt are similar to wild-type, maximal +dP/dt and -dP/dt at 18-22 weeks are reduced following isoproterenol infusion

• maximal contraction amplitude is lower than wild-type at 5 mM [Ca²⁺]

increased heart ventricle muscle contractility ( J:182365 )

• increased ejection fraction

nervous system

abnormal action potential ( J:182365 )

• action potential duration is doubled, however, resting E_m and action potential amplitude are similar to controls

Genotype
MGI:3819379

cx12

• Allelic Composition: Tg(Myh6/tetO-POSTN)22.1Jmol/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: FVB/N

cardiovascular system

cardiovascular system phenotype ( J:140301 )

N • despite cardiac hypertrophy, mice exhibit normal ventricular performance

increased heart weight ( J:140301 )

• by 24 weeks of age, ventricular weight normalized to body weight is increased compared to in wild-type mice

cardiac hypertrophy ( J:140301 )

• by 24 weeks of age, mice exhibit cardiac hypertrophy compared to wild-type mice

• following transverse aortic constriction to induce pressure overload, mice exhibit more cardiac hypertrophy with increased myocyte cross-section diameter after 8 weeks compared to similarly treated wild-type mice

abnormal response to cardiac infarction ( J:140301 )

• mice are protected from ventricular wall rupture following induced myocardial infarct unlike wild-type mice

homeostasis/metabolism

abnormal response to cardiac infarction ( J:140301 )

• mice are protected from ventricular wall rupture following induced myocardial infarct unlike wild-type mice

increased susceptibility to injury ( J:140301 )

• following transverse aortic constriction to induce pressure overload, mice exhibit more cardiac hypertrophy with increased myocyte cross-section diameter after 8 weeks compared to similarly treated wild-type mice

growth/size/body

increased heart weight ( J:140301 )

• by 24 weeks of age, ventricular weight normalized to body weight is increased compared to in wild-type mice

cardiac hypertrophy ( J:140301 )

• by 24 weeks of age, mice exhibit cardiac hypertrophy compared to wild-type mice

• following transverse aortic constriction to induce pressure overload, mice exhibit more cardiac hypertrophy with increased myocyte cross-section diameter after 8 weeks compared to similarly treated wild-type mice

Genotype
MGI:3851897

cx13

• Allelic Composition: Tg(Myh6-tTA)55Rbns/0; Tg(Myh6/tetO-PRKCA*)1Jmk/0
• Genetic Background: involves: FVB/N

cardiovascular system

abnormal myocardium layer morphology ( J:132098 )

• induced mice show equivalent infarcted area/area at risk ratio to wild-type after myocardial infarction

increased heart weight ( J:132098 )

• by 16 weeks after MI, wild-type mice show significant increases in heart weight/body weight ratios, but induced mutants exhibit partial protection from changes

abnormal cardiac muscle contractility ( J:132098 )

• induced mice show greater fractional shortening (%) than wild-type up to 3 weeks after myocardial infarction (MI)

increased heart ventricle muscle contractility ( J:132098 )

• induced adult mice (no doxycycline) showed increased contractility at baseline and with dobutamine infusion compared with wild-type mice; mutant mice treated with doxycycline show no increased contractility compared to wild-type

• by 12 and 16 weeks after MI, induced mice show reduced ventricular performance similar to wild-type with MI

• induced mice show greater fractional shortening (%) than wild-type up to 3 weeks after myocardial infarction (MI)

• after experimental myocardial infarction (MI), uninduced mice (doxycycline treated) showed decreased ventricular function whereas mice without doxycycline (induced) show partial protection against functional performance deficits at 1 and 2 weeks following MI

muscle

abnormal myocardium layer morphology ( J:132098 )

• induced mice show equivalent infarcted area/area at risk ratio to wild-type after myocardial infarction

abnormal cardiac muscle contractility ( J:132098 )

• induced mice show greater fractional shortening (%) than wild-type up to 3 weeks after myocardial infarction (MI)

increased heart ventricle muscle contractility ( J:132098 )

• induced adult mice (no doxycycline) showed increased contractility at baseline and with dobutamine infusion compared with wild-type mice; mutant mice treated with doxycycline show no increased contractility compared to wild-type

• by 12 and 16 weeks after MI, induced mice show reduced ventricular performance similar to wild-type with MI

• induced mice show greater fractional shortening (%) than wild-type up to 3 weeks after myocardial infarction (MI)

• after experimental myocardial infarction (MI), uninduced mice (doxycycline treated) showed decreased ventricular function whereas mice without doxycycline (induced) show partial protection against functional performance deficits at 1 and 2 weeks following MI

growth/size/body

increased heart weight ( J:132098 )

• by 16 weeks after MI, wild-type mice show significant increases in heart weight/body weight ratios, but induced mutants exhibit partial protection from changes

Genotype
MGI:3851933

cx14

• Allelic Composition: Tg(Myh6-tTA)55Rbns/0; Tg(tetO-Dusp6)1Jmol/0
• Genetic Background: involves: FVB/N

cardiovascular system

increased myocardial fiber size ( J:124903 )

• similar increase in myocyte cross-sectional area in left ventricle is observed in induced transgenic mice and controls after angiotensin II and isoproterenol infusion

cardiac hypertrophy ( J:124903 )

• induced (removal of doxycycline treatment) mice show the same hypertrophic response to procedures such as transverse aortic constriction (TAC) and forced exercise as wild-type and single transgenic controls

• hypertrophy in response to agonists such as angiotensin II and isoproterenol is identical to that seen in treated wild-type after 14 days

cardiac fibrosis ( J:124903 )

• after 14 days of isoproterenol infusion, mice display 2-fold greater fibrosis than control mice

decreased cardiac muscle contractility ( J:124903 )

• medium- and high-expressing transgenic mice show significantly greater decompensation after 14 weeks of transverse aortic constriction compared to wild-type

muscle

increased myocardial fiber size ( J:124903 )

• similar increase in myocyte cross-sectional area in left ventricle is observed in induced transgenic mice and controls after angiotensin II and isoproterenol infusion

decreased cardiac muscle contractility ( J:124903 )

• medium- and high-expressing transgenic mice show significantly greater decompensation after 14 weeks of transverse aortic constriction compared to wild-type

increased cardiomyocyte apoptosis ( J:124903 )

• 1 week of acute pressure overload caused increased TUNEL rates in high- and medium-expressing mice and remain elevated after 14 weeks of TAC in high-expressing mice

respiratory system

abnormal respiratory system physiology ( J:124903 )

cellular

increased cardiomyocyte apoptosis ( J:124903 )

• 1 week of acute pressure overload caused increased TUNEL rates in high- and medium-expressing mice and remain elevated after 14 weeks of TAC in high-expressing mice

growth/size/body

cardiac hypertrophy ( J:124903 )

• induced (removal of doxycycline treatment) mice show the same hypertrophic response to procedures such as transverse aortic constriction (TAC) and forced exercise as wild-type and single transgenic controls

• hypertrophy in response to agonists such as angiotensin II and isoproterenol is identical to that seen in treated wild-type after 14 days

Genotype
MGI:4430402

cx15

• Allelic Composition: Tg(Myh6-Gnaq)#Gwd/0; Tg(Myh6-tTA)55Rbns/0; Tg(tetO-Bnip3l)1Gwd/0
• Genetic Background: involves: FVB/N

mortality/aging

premature death ( J:145086 )

• all mice die between 6 and 8 weeks after birth

cardiovascular system

abnormal heart ventricle morphology ( J:145086 )

• mice exhibit ventricular remodeling as measured by the ratio of the ventricular radius to wall thickness unlike in wild-type mice

decreased cardiac muscle contractility ( J:145086 )

• drastically

muscle

decreased cardiac muscle contractility ( J:145086 )

• drastically

increased cardiomyocyte apoptosis ( J:145086 )

cellular

increased cardiomyocyte apoptosis ( J:145086 )

Genotype
MGI:4430403

cx16

• Allelic Composition: Tg(Myh6-tTA)55Rbns/0; Tg(tetO-Bnip3l)1Gwd/0
• Genetic Background: involves: FVB/N

cardiovascular system

cardiovascular system phenotype ( J:145086 )

N • mice do not exhibit ventricular remodeling

decreased cardiac muscle contractility ( J:145086 )

• over time

muscle

decreased cardiac muscle contractility ( J:145086 )

• over time

increased cardiomyocyte apoptosis ( J:145086 )

cellular

increased cardiomyocyte apoptosis ( J:145086 )

Genotype
MGI:5780592

cx17

• Allelic Composition: Tg(Myh6*/tetO-Slc8a1)BJych/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: FVB/N

cardiovascular system

abnormal myocardial fiber morphology ( J:151091 )

• sarcoplasmic reticulum Ca²⁺ content at 5.0 mM is higher than controls

abnormal cardiac muscle contractility ( J:151091 )

• increased contraction amplitude in response to elevation of Ca²⁺ as compared to controls

• at 0.6 mM [Ca²⁺] myocytes shorten less than controls

• at 5.0 mM [Ca²⁺] myocytes contract more than controls

• at 1.8 mM [Ca²⁺] contraction amplitudes are similar controls

• maximal shortening and relengthening velocities are both slower (at 0.6) and faster (at 5.0) than controls

• systolic and transient amplitudes are both lower (at 0.6) and higher (at 5.0) than controls, however, there is no difference in diastolic amplitude

abnormal myocardial fiber physiology ( J:151091 )

• increased I_NaCa (NCX1 current) in myocytes as voltage becomes more positive as compared to controls

muscle

abnormal myocardial fiber morphology ( J:151091 )

• sarcoplasmic reticulum Ca²⁺ content at 5.0 mM is higher than controls

abnormal cardiac muscle contractility ( J:151091 )

• increased contraction amplitude in response to elevation of Ca²⁺ as compared to controls

• at 0.6 mM [Ca²⁺] myocytes shorten less than controls

• at 5.0 mM [Ca²⁺] myocytes contract more than controls

• at 1.8 mM [Ca²⁺] contraction amplitudes are similar controls

• maximal shortening and relengthening velocities are both slower (at 0.6) and faster (at 5.0) than controls

• systolic and transient amplitudes are both lower (at 0.6) and higher (at 5.0) than controls, however, there is no difference in diastolic amplitude

nervous system

abnormal action potential ( J:151091 )

• action potential duration is prolonged at 50% and 90% repolarization as compared to controls

Genotype
MGI:5909973

cx18

• Allelic Composition: Tg(Myh6/tetO-Mybpc3*)#Rbns/0; Tg(Myh6-tTA)55Rbns/0
• Genetic Background: involves: FVB/N

mortality/aging

premature death ( J:213370 )

• mice being to die as early as 23 days after birth, with the majority of mice deceased by 8 weeks

• mice treated with the MEK inhibitor U0126 show increases in lifespan and survival

cardiovascular system

abnormal heart morphology ( J:213370 )

• aberrant cardiac morphology is seen at 12 weeks, with perturbed chamber arrangement and overall geometry

increased heart atrium size ( J:213370 )

• atrial enlargement at 12 weeks

increased heart weight ( J:213370 )

• ratio of heart weight-to-body weight is increased

abnormal heart left ventricle morphology ( J:213370 )

• increase in left ventricular mass

• mice treated with U0126 show improved left ventricular mass and diastolic volumes

increased heart ventricle size ( J:213370 )

• ventricular enlargement at 12 weeks

cardiac fibrosis ( J:213370 )

• cardiac fibrosis is seen as early as 4 weeks and progressively increases with age

abnormal cardiovascular system physiology ( J:213370 )

• mice begin showing overt signs of cardiac dysfunction in early adulthood

decreased cardiac muscle contractility ( J:213370 )

• fractional shortening is decreased after 12 weeks of age

• mice treated with the MEK inhibitor U0126 show improved fractional shortening

congestive heart failure ( J:213370 )

• mice exhibit obvious signs of heart failure, including anasarca, fluid retention, and listlessness

muscle

decreased cardiac muscle contractility ( J:213370 )

• fractional shortening is decreased after 12 weeks of age

• mice treated with the MEK inhibitor U0126 show improved fractional shortening

abnormal muscle fiber morphology ( J:213370 )

• overall architecture of the mitochondria is severely disrupted in hearts

abnormal sarcomere morphology ( J:213370 )

• sarcomeres are out of register and normal pattern organization is disrupted in hearts

growth/size/body

increased heart weight ( J:213370 )

• ratio of heart weight-to-body weight is increased

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 4		DOID:0110310	OMIM:115197	J:213370

Genotype
MGI:3841180

cx19

• Allelic Composition: Tg(Myh6-tTA)55Rbns/0; Tg(Myh6/tetO-PRKAG2*N488I)1Chib/0
• Genetic Background: Not Specified

cardiovascular system

increased cardiac muscle glycogen level ( J:145090 )

• myocardial glycogen content is 30-fold higher than in wild-type mice

• however, doxycycline treatment reduces myocardial glycogen content

abnormal heart morphology ( J:145090 )

• the anulus fibrosus that separates the atria from ventricles is discontinuous compared to in wild-type mice

• the anulus fibrosus in mice treated with doxycycline between 4 and 16 weeks is disrupted and disorganized without vacuolization of the septal and left ventricular wall myocytes

• however, the anulus fibrosus is intact in mice treated early with doxycycline (prenatal to 8 weeks)

abnormal myocardial fiber morphology ( J:145090 )

• unlike in wild-type mice, vacuoles are present in the myocytes of the right ventricle in mice treated with doxycycline between 4 and 16 weeks

heart left ventricle hypertrophy ( J:145090 )

• at 16 weeks

abnormal heart septum morphology ( J:145090 )

• hypertrophic at 8 weeks of age

increased heart weight ( J:145090 )

• heart weight is increased compared to in wild-type mice

• however, doxycycline treatment reduces heart weight 30% compared to in untreated mice

abnormal heart right ventricle morphology ( J:145090 )

• unlike in wild-type mice, vacuoles are present in the myocytes of the right ventricle in mice treated with doxycycline between 4 and 16 weeks

thick ventricular wall ( J:145090 )

• mice exhibit increased ventricular wall thickness compared to in wild-type mice

• early doxycycline treatment (prenatally to 8 weeks of age) delays myocardial wall thickening

• however, doxycycline treatment reduces ventricular wall thickness irregardless of treatment time

decreased heart left ventricle muscle contractility ( J:145090 )

• at 16 weeks, mice exhibit progressive systolic dysfunction indicated by increased left ventricle end diastolic diameter and decreased fractional shortening unlike wild-type mice

• however, doxycycline treatment ameliorates myocardial dysfunction

decreased heart rate ( J:145090 )

• mice exhibit decreased heart rates compared to in wild-type mice regardless of doxycycline treatment

increased heart rate ( J:145090 )

• 50% of mice frequently exhibit supraventricular tachycardia

• however, mice treated early (prenatal to 8 weeks) with doxycycline do not develop supraventricular tachycardia

abnormal impulse conducting system conduction ( J:145090 )

• mice exhibit preexcitation unlike in wild-type mice

• early doxycycline treatment (prenatally to 8 weeks of age) delays myocardial dysfunction

• doxycycline-treatment between 4 and 16 weeks results in a decline of preexcitation from 50% to 11% and is accompanied by atrial pacing

• doxycycline treatment after 8 weeks does not cause loss of preexcitation or alter the electrical properties of accessory pathways

• however, prenatal or early treatment with doxyxycline through 8 weeks of age prevents preexcitation while late treatment (after 20 weeks) improves cardiac conduction system function

• however, mice exhibit normal cardiac conduction velocity regardless of doxycycline treatment

shortened PR interval ( J:145090 )

• at 4 weeks, the PR interval is shortened in 50% to 60% of mice compared to in wild-type mice

atrioventricular block ( J:145090 )

• AV conduction properties are 50% prolonged compared to in wild-type mice

• 1 of 8 mice exhibited intermittent complete AV block

• early doxycycline suppression (prenatally to 8 weeks of age) does not improve sinus and atrioventriular node abnormalities

abnormal QRS complex ( J:145090 )

• at 4 weeks, 50% to 60% of mice exhibit prolonged, slurred-upstroke QRS complexes unlike in wild-type mice

prolonged QRS complex duration ( J:145090 )

sinoatrial block ( J:145090 )

• 30% of mice exhibit sinoatrial exit block unlike in wild-type mice

• early doxycycline suppression (prenatally to 8 weeks of age) does not improve sinus and atrioventriular node abnormalities

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:145090 )

• myocardial glycogen content is 30-fold higher than in wild-type mice

• however, doxycycline treatment reduces myocardial glycogen content

muscle

increased cardiac muscle glycogen level ( J:145090 )

• myocardial glycogen content is 30-fold higher than in wild-type mice

• however, doxycycline treatment reduces myocardial glycogen content

abnormal myocardial fiber morphology ( J:145090 )

• unlike in wild-type mice, vacuoles are present in the myocytes of the right ventricle in mice treated with doxycycline between 4 and 16 weeks

heart left ventricle hypertrophy ( J:145090 )

• at 16 weeks

decreased heart left ventricle muscle contractility ( J:145090 )

• at 16 weeks, mice exhibit progressive systolic dysfunction indicated by increased left ventricle end diastolic diameter and decreased fractional shortening unlike wild-type mice

• however, doxycycline treatment ameliorates myocardial dysfunction

growth/size/body

heart left ventricle hypertrophy ( J:145090 )

• at 16 weeks

increased heart weight ( J:145090 )

• heart weight is increased compared to in wild-type mice

• however, doxycycline treatment reduces heart weight 30% compared to in untreated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lethal congenital glycogen storage disease of heart		DOID:0090101	OMIM:261740	J:145090

Genotype
MGI:3764675

cx20

• Allelic Composition: Tg(Myh6-tTA)55Rbns/?; Tg(Myh6/tetO-BNIP3)1Gwd/?
• Genetic Background: Not Specified

cardiovascular system

increased heart weight ( J:127533 )

• when expression begins neonatally, heart weight is increased (8.7+/-0.9 mg/g compared to 5.7+/-0.3 mg/g in wild-type mice)

dilated heart left ventricle ( J:127533 )

• whether expression begins neonatally or at 8 weeks of age, neonates develop progressive left ventricle dilation that is not as severe in adulthood

decreased left ventricle systolic pressure ( J:127533 )

• whether expression begins neonatally or at 8 weeks of age, left ventricle systolic pressure is decreased compared to in wild-type mice

increased myocardial infarct size ( J:127533 )

• whether expression begins neonatally or at 8 weeks of age, infarct size is larger than in wild-type mice

muscle

increased cardiomyocyte apoptosis ( J:127533 )

• whether expression begins neonatally or at 8 weeks of age, apoptotic rate in the heart is increased 5- to 10-fold at 10 or 40 weeks of age

homeostasis/metabolism

increased myocardial infarct size ( J:127533 )

• whether expression begins neonatally or at 8 weeks of age, infarct size is larger than in wild-type mice

cellular

increased cardiomyocyte apoptosis ( J:127533 )

• whether expression begins neonatally or at 8 weeks of age, apoptotic rate in the heart is increased 5- to 10-fold at 10 or 40 weeks of age

growth/size/body

increased heart weight ( J:127533 )

• when expression begins neonatally, heart weight is increased (8.7+/-0.9 mg/g compared to 5.7+/-0.3 mg/g in wild-type mice)

Genotype
MGI:3757977

cx21

• Allelic Composition: Tg(Myh6-tTA)55Rbns/0; Tg(Myh6/tetO-Gsk3b*S9A)1Rbns/0
• Genetic Background: Not Specified

cardiovascular system

decreased response of heart to induced stress ( J:125131 )

• the normal hypertrophic response to transaortic coarctation (TAC) is blunted in double transgenics in the absence of Dox; when transgenics are kept on Dox and Gsk3b expression is suppressed, they develop hypertrophy comparable to that of controls

homeostasis/metabolism

decreased response of heart to induced stress ( J:125131 )

• the normal hypertrophic response to transaortic coarctation (TAC) is blunted in double transgenics in the absence of Dox; when transgenics are kept on Dox and Gsk3b expression is suppressed, they develop hypertrophy comparable to that of controls

Genotype
MGI:3758000

cx22

• Allelic Composition: Tg(Myh6-tTA)55Rbns/0; Tg(Myh6*/tetO-GCaMP2)1Mik/0
• Genetic Background: Not Specified

cardiovascular system

enlarged heart ( J:107637 )

• cardiomegaly develops in adults in the absence of dox (unregulated expression of GCaMP2); double transgenics maintained on dox have normal heart size

growth/size/body

enlarged heart ( J:107637 )

• cardiomegaly develops in adults in the absence of dox (unregulated expression of GCaMP2); double transgenics maintained on dox have normal heart size