Phenotypes associated with this allele

• Allele Symbol: Tg(Myh6-cre)1Xya
• Allele Name: transgene insertion 1, Xiao Yang
• Allele ID: MGI:3690221
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Akt1^tm1Zzy/Akt1^tm1Zzy Akt3^tm1Hem/Akt3^tm1Hem Tg(Myh6-cre)1Xya/0	involves: 129P2/OlaHsd * FVB	MGI:5563578
cn2	Wdr1^tm1.1Zzy/Wdr1^+ Tg(Myh6-cre)1Xya/0	involves: 129S6/SvEvTac * C57BL/6J	MGI:5688485
cn3	Wdr1^tm1.1Zzy/Wdr1^tm1.1Zzy Tg(Myh6-cre)1Xya/0	involves: 129S6/SvEvTac * C57BL/6J	MGI:5688486
cn4	Rbm24^tm1.1Xixu/Rbm24^tm1.1Xixu Tg(Myh6-cre)1Xya/0	involves: C57BL/6NTac	MGI:7408196

Genotype
MGI:5563578

cn1

• Allelic Composition: Akt1^tm1Zzy/Akt1^tm1Zzy; Akt3^tm1Hem/Akt3^tm1Hem; Tg(Myh6-cre)1Xya/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

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

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:206783 )

• following myocardial infarction, rapamycin-treated mice exhibit reduced heart weight compared with untreated mice

• however, rapamycin treatment following myocardial infarction fail to exhibit a change in fibrotic index, ejection fraction, fractional shortening or left ventricular internal diameter at end-diastole

cardiovascular system

decreased heart weight ( J:206783 )

• following myocardial infarction, rapamycin-treated mice exhibit reduced heart weight compared with untreated mice

Genotype
MGI:5688485

cn2

• Allelic Composition: Wdr1^tm1.1Zzy/Wdr1⁺; Tg(Myh6-cre)1Xya/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:211364 )

• mice are healthy and fertile

Genotype
MGI:5688486

cn3

• Allelic Composition: Wdr1^tm1.1Zzy/Wdr1^tm1.1Zzy; Tg(Myh6-cre)1Xya/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

mortality/aging

premature death ( J:211364 )

• no mice survive past P24

postnatal lethality, incomplete penetrance ( J:211364 )

• although born phenotypically normal and at the expected Mendelian ratios, mice begin to die from P13 often of sudden death

cardiovascular system

abnormal myocardium layer morphology ( J:211364 )

• at P10, mice exhibit mild F-actin accumulations in the myocardium relative to wild-type controls

• large amounts of F-actin accumulations are noted at P12, with further increases at P14

abnormal myocardial fiber morphology ( J:211364 )

• at P12, mutant myofibrils show severe disruption of the sarcomeric structure; the sarcomeric structural component alpha-actinin and the F-actin pointed end capping protein Tmod1 are not aligned in a striated pattern in regions with strong F-actin accumulations, unlike in control mice

• within actin aggregates, sarcomeric alpha-actinin staining is strongly reduced and Tmod1 staining is diffused but robust

• at P12, TEM analysis of mutant cardiac muscle showed a normal looking structure, with distinct A bands and narrow and uniformly spaced Z lines, and no evidence of nemaline bodies; however, strong F-actin accumulations were found in areas of myofibrillar disruption

• Western blotting analysis showed increased cardiac levels of sarcomeric proteins (Tmod1, cardiac troponin T, cardiac troponin I, tropomyosin, pan-actin), and total cofilin, but not of sarcomeric alpha-actinin

• total cofilin is abundant in myofibrils where F-actin accumulations are present

• at P10, qPCR analysis revealed that mRNA expression levels of alpha-skeletal muscle actin and aortic smooth muscle actin are significantly increased and those of alpha-cardiac muscle actin-1 are decreased

increased myocardial fiber size ( J:211364 )

• starting at P12, mutant cardiomyocytes are significantly larger, indicating hypertrophic growth of cardiomyocytes

• however, no significant changes in cell proliferation and apoptosis are observed, as shown by Ki-67 and TUNEL staining

abnormal interventricular septum morphology ( J:211364 )

• interventricular septum in diastole begins to increase at P10

enlarged heart ( J:211364 )

• starting at P12, mice exhibit a larger heart than control mice

increased heart weight ( J:211364 )

• starting at P12, mice show a significant increase in heart weight/body weight ratio relative to control mice

• however, body weight remains normal from birth to death

cardiac hypertrophy ( J:211364 )

• at P12, mutant hearts show markedly increased mRNA levels of the hypertrophic markers ANP and BNP, unlike control hearts

abnormal heart left ventricle morphology ( J:211364 )

• left ventricular internal dimension in diastole begins to decrease at P10

decreased heart left ventricle muscle contractility ( J:211364 )

• at P12, mutant hearts exhibit a significantly decreased LV fractional shortening (FS) and LV ejection fraction (EF) relative to control hearts

• EF, FS and left ventricular internal dimension in diastole begin to decrease and interventricular septum in diastole begins to increase at P10

decreased heart rate ( J:211364 )

• at P10, mice show a significant decrease in heart rate (417 +/- 11 bpm) relative to controls (447 +/- 19 bpm)

• at P12, the heart rate is further reduced (383 +/- 39 bpm) relative to controls (453 +/- 58 bpm)

abnormal heart electrocardiography waveform feature ( J:211364 )

• mice exhibit alterations in the QT interval, ST height, and T-wave amplitude indicating abnormalities of ventricular electrocardiographic repolarization

prolonged P wave ( J:211364 )

• starting at P10, mice display prolonged P duration relative to control mice

• however, no differences are detected in the PR interval or QRS waves at P10 and P12

prolonged QT interval ( J:211364 )

• starting at P12, mice display a prolonged QT interval relative to control mice

prolonged ST segment ( J:211364 )

• starting at P12, mice display an elevated ST height relative to control mice

abnormal T wave ( J:211364 )

• starting at P10, mice show a significant increase in T-wave amplitude relative to control mice

muscle

abnormal myocardium layer morphology ( J:211364 )

• at P10, mice exhibit mild F-actin accumulations in the myocardium relative to wild-type controls

• large amounts of F-actin accumulations are noted at P12, with further increases at P14

abnormal myocardial fiber morphology ( J:211364 )

• at P12, mutant myofibrils show severe disruption of the sarcomeric structure; the sarcomeric structural component alpha-actinin and the F-actin pointed end capping protein Tmod1 are not aligned in a striated pattern in regions with strong F-actin accumulations, unlike in control mice

• within actin aggregates, sarcomeric alpha-actinin staining is strongly reduced and Tmod1 staining is diffused but robust

• at P12, TEM analysis of mutant cardiac muscle showed a normal looking structure, with distinct A bands and narrow and uniformly spaced Z lines, and no evidence of nemaline bodies; however, strong F-actin accumulations were found in areas of myofibrillar disruption

• Western blotting analysis showed increased cardiac levels of sarcomeric proteins (Tmod1, cardiac troponin T, cardiac troponin I, tropomyosin, pan-actin), and total cofilin, but not of sarcomeric alpha-actinin

• total cofilin is abundant in myofibrils where F-actin accumulations are present

• at P10, qPCR analysis revealed that mRNA expression levels of alpha-skeletal muscle actin and aortic smooth muscle actin are significantly increased and those of alpha-cardiac muscle actin-1 are decreased

increased myocardial fiber size ( J:211364 )

• starting at P12, mutant cardiomyocytes are significantly larger, indicating hypertrophic growth of cardiomyocytes

• however, no significant changes in cell proliferation and apoptosis are observed, as shown by Ki-67 and TUNEL staining

decreased heart left ventricle muscle contractility ( J:211364 )

• at P12, mutant hearts exhibit a significantly decreased LV fractional shortening (FS) and LV ejection fraction (EF) relative to control hearts

• EF, FS and left ventricular internal dimension in diastole begin to decrease and interventricular septum in diastole begins to increase at P10

growth/size/body

enlarged heart ( J:211364 )

• starting at P12, mice exhibit a larger heart than control mice

increased heart weight ( J:211364 )

• starting at P12, mice show a significant increase in heart weight/body weight ratio relative to control mice

• however, body weight remains normal from birth to death

cardiac hypertrophy ( J:211364 )

• at P12, mutant hearts show markedly increased mRNA levels of the hypertrophic markers ANP and BNP, unlike control hearts

Genotype
MGI:7408196

cn4

• Allelic Composition: Rbm24^tm1.1Xixu/Rbm24^tm1.1Xixu; Tg(Myh6-cre)1Xya/0
• Genetic Background: involves: C57BL/6NTac

mortality/aging

premature death ( J:302917 )

• mice start to die at P11 and all die before 2 months of age

postnatal lethality, incomplete penetrance ( J:302917 )

• earliest time of death is at P11

growth/size/body

weight loss ( J:302917 )

• mice exhibit weight loss and smaller body size with increasing age

respiratory system

respiratory distress ( J:302917 )

• mice exhibit shortness of breath with increasing age

cardiovascular system

dilated heart ventricle ( J:302917 )

• mice show increased dilation of the ventricle chambers at P5

cardiac fibrosis ( J:302917 )

• mice show increased cardiac fibrosis at P5

dilated cardiomyopathy ( J:302917 )

• mice exhibit dilated cardiomyopathy by P23

decreased heart left ventricle muscle contractility ( J:302917 )

• mice show a decrease in left ventricular systolic function, showing a decrease in fractional shortening and ejection fraction, at P23

abnormal heart echocardiography feature ( J:302917 )

• echocardiography at P23 shows enlarged left ventricular chamber size, wall thinning, decreased interventricular septal thickness at end systole and decreased left ventricular posterior wall thickness at end systole, and an increase in left ventricular internal diameter during both systole and diastole

congestive heart failure ( J:302917 )

• mice develop heart failure

• congestion in the left ventricle and left atrium of hearts is seen after death

behavior/neurological

hypoactivity ( J:302917 )

• mice exhibit decreased spontaneous activity preceding death

muscle

dilated cardiomyopathy ( J:302917 )

• mice exhibit dilated cardiomyopathy by P23

decreased heart left ventricle muscle contractility ( J:302917 )

• mice show a decrease in left ventricular systolic function, showing a decrease in fractional shortening and ejection fraction, at P23

abnormal sarcomere morphology ( J:302917 )

• sarcomere structure of heart shows minor defects at P5 but major alterations in myocardial structure at P23, including less, substantially short and dramatic disarrayed sarcomeres, irregular and wavy Z-disc and M-band

abnormal M line morphology ( J:302917 )

• the M-band is irregular and wavy in myocardium at P23

abnormal Z line morphology ( J:302917 )

• irregular and wavy Z-disc and distribution of Z-disc is affected in myocardium at P23

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:302917