Phenotypes associated with this allele

• Allele Symbol: Myoz2^tm1Eno
• Allele Name: targeted mutation 1, Eric N Olson
• Allele ID: MGI:3525108
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Myoz2^tm1Eno/Myoz2^tm1Eno	involves: 129 * C57BL/6J	MGI:3525235
cx2	Myoz2^tm1Eno/Myoz2^tm1Eno Tg(Myh6-Ppp3ca)37Eno/0	involves: 129 * C57BL/6J	MGI:3525242
cx3	Myoz2^tm1Eno/Myoz2^+ Tg(Myh6-MYOZ2*I246M)#Ajm/0	involves: 129/Sv * FVB/N	MGI:5581492

Genotype
MGI:3525235

hm1

• Allelic Composition: Myoz2^tm1Eno/Myoz2^tm1Eno
• Genetic Background: involves: 129 * C57BL/6J

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

cardiovascular system

abnormal myocardial fiber morphology ( J:94665 )

• Z-discs in homozygous mutant hearts appeared fuzzy and widened and showed a significant 36% increase in diameter

decreased myocardial fiber size ( J:94665 )

• cross-sectional area of cardiomyocytes from 3 week old mutants was reduced compared to wild-type, however at older ages, differences in the area were not observed

dilated heart atrium ( J:94665 )

• after 3 weeks of aortic banding (causing pressure overload), showed dilation of the atria

enlarged heart ( J:94665 )

• hearts from homozygotes were indistinguishable from wild-type under normal conditions, however when subjected to stress via aortic banding, the heart was enlarged compared to wild-type

cardiac hypertrophy ( J:94665 )

• although homozygotes did not develop spontaneous cardiac hypertrophy (under non-stressful conditions), the hypertrophic gene program was chronically activated in mutants

• homozygotes subjected to pressure overload via thoracic aortic banding showed a higher increase in cardiac mass than controls (58% increase in heart weight/body weight ratio versus 27% increase in wild-type) but not when chronically stimulated with an adrenergic agonist

dilated heart left ventricle ( J:94665 )

• after 3 weeks of aortic banding (causing pressure overload), showed dilation of both ventricles

dilated heart right ventricle ( J:94665 )

• after 3 weeks of aortic banding (causing pressure overload), showed dilation of both ventricles

abnormal cardiovascular system physiology ( J:94665 )

decreased cardiac muscle contractility ( J:94665 )

• systolic dysfunction with fractional shortening of 35.9% in homozygous mutants compared to 46.7% in controls but no differences in left ventricular end diastolic diameters

• reduction in the ejection fraction (49.2% versus 59.2% of blood that is pumped out of a filled ventricle) was observed by cardiac catheterization

• end diastolic (46.5 versus 38.2 ul) and end systolic (26.5 versus 17 ul) volumes were elevated however end diastolic and systolic pressures were unchanged

increased response of heart to induced stress ( J:94665 )

• homozygotes subjected to pressure overload via thoracic aortic banding exhibit increased cardiac hypertrophy and cardiomyopathy compared to wild-type

cardiomyopathy ( J:94665 )

• after 3 weeks of aortic banding (causing pressure overload), showed exacerbated cardiomyopathy

muscle

abnormal myocardial fiber morphology ( J:94665 )

• Z-discs in homozygous mutant hearts appeared fuzzy and widened and showed a significant 36% increase in diameter

decreased myocardial fiber size ( J:94665 )

• cross-sectional area of cardiomyocytes from 3 week old mutants was reduced compared to wild-type, however at older ages, differences in the area were not observed

decreased cardiac muscle contractility ( J:94665 )

• systolic dysfunction with fractional shortening of 35.9% in homozygous mutants compared to 46.7% in controls but no differences in left ventricular end diastolic diameters

• reduction in the ejection fraction (49.2% versus 59.2% of blood that is pumped out of a filled ventricle) was observed by cardiac catheterization

• end diastolic (46.5 versus 38.2 ul) and end systolic (26.5 versus 17 ul) volumes were elevated however end diastolic and systolic pressures were unchanged

cardiomyopathy ( J:94665 )

• after 3 weeks of aortic banding (causing pressure overload), showed exacerbated cardiomyopathy

abnormal skeletal muscle morphology ( J:94665 )

decreased skeletal muscle fiber size ( J:94665 )

• the size of slow-fibers was decreased in soleus muscle

abnormal skeletal muscle fiber type ratio ( J:94665 )

• the number of type I (slow) skeletal muscle fibers was significantly increased (439 versus 289 in wild-type) in soleus muscle

homeostasis/metabolism

increased response of heart to induced stress ( J:94665 )

• homozygotes subjected to pressure overload via thoracic aortic banding exhibit increased cardiac hypertrophy and cardiomyopathy compared to wild-type

growth/size/body

enlarged heart ( J:94665 )

• hearts from homozygotes were indistinguishable from wild-type under normal conditions, however when subjected to stress via aortic banding, the heart was enlarged compared to wild-type

cardiac hypertrophy ( J:94665 )

• although homozygotes did not develop spontaneous cardiac hypertrophy (under non-stressful conditions), the hypertrophic gene program was chronically activated in mutants

• homozygotes subjected to pressure overload via thoracic aortic banding showed a higher increase in cardiac mass than controls (58% increase in heart weight/body weight ratio versus 27% increase in wild-type) but not when chronically stimulated with an adrenergic agonist

Genotype
MGI:3525242

cx2

• Allelic Composition: Myoz2^tm1Eno/Myoz2^tm1Eno; Tg(Myh6-Ppp3ca)37Eno/0
• Genetic Background: involves: 129 * C57BL/6J

mortality/aging

premature death ( J:94665 )

• died by 20-28 days of age

cardiovascular system

increased myocardial fiber size ( J:94665 )

• 110% increase in myocyte size compared to a 34% increase in mice expressing only the transgene

cardiac hypertrophy ( J:94665 )

• showed massive cardiac enlargement that exceeded the hypertrophy induced by the transgene alone

• at 3 weeks of age, 244% increase in heart weight/body weight ratio compared to a 149% increase in mice expressing only the transgene

muscle

increased myocardial fiber size ( J:94665 )

• 110% increase in myocyte size compared to a 34% increase in mice expressing only the transgene

growth/size/body

cardiac hypertrophy ( J:94665 )

• showed massive cardiac enlargement that exceeded the hypertrophy induced by the transgene alone

• at 3 weeks of age, 244% increase in heart weight/body weight ratio compared to a 149% increase in mice expressing only the transgene

Genotype
MGI:5581492

cx3

• Allelic Composition: Myoz2^tm1Eno/Myoz2⁺; Tg(Myh6-MYOZ2*I246M)#Ajm/0
• Genetic Background: involves: 129/Sv * FVB/N

cardiovascular system

increased myocardial fiber size ( J:210073 )

• increase in cross-sectional area of cardiac myocytes

thick interventricular septum ( J:210073 )

cardiac hypertrophy ( J:210073 )

• ventricular/body weight ratio is increased, indicating cardiac hypertrophy

• molecular markers of cardiac hypertrophy (Myh7 and Nppb) are increased

heart left ventricle hypertrophy ( J:210073 )

• mice exhibit left ventricular hypertrophy as indicated by increased interventricular septal thickness and left ventricular mass

thick ventricular wall ( J:210073 )

• increase in posterior wall thickness

cardiac interstitial fibrosis ( J:210073 )

• 2-fold increase in interstitial fibrosis

• molecular markers of fibrosis (Co1a1 and Col3a1) are increased

abnormal cardiovascular system physiology ( J:210073 )

• left ventricular end diastolic diameter is moderately increased and mitral inflow is increased

• however left ventricular systolic function is normal

muscle

increased myocardial fiber size ( J:210073 )

• increase in cross-sectional area of cardiac myocytes

heart left ventricle hypertrophy ( J:210073 )

• mice exhibit left ventricular hypertrophy as indicated by increased interventricular septal thickness and left ventricular mass

abnormal Z line morphology ( J:210073 )

• various Z disk abnormalities, including poorly formed Z disks associated with myofibrillar disarray, and interrupted, discontinuous, bulging and slipped Z disks

growth/size/body

cardiac hypertrophy ( J:210073 )

• ventricular/body weight ratio is increased, indicating cardiac hypertrophy

• molecular markers of cardiac hypertrophy (Myh7 and Nppb) are increased

heart left ventricle hypertrophy ( J:210073 )

• mice exhibit left ventricular hypertrophy as indicated by increased interventricular septal thickness and left ventricular mass

cellular

cardiac interstitial fibrosis ( J:210073 )

• 2-fold increase in interstitial fibrosis

• molecular markers of fibrosis (Co1a1 and Col3a1) are increased

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrophic cardiomyopathy 16		DOID:0110322	OMIM:613838	J:210073