Phenotypes Associated with This Genotype

Genotype
MGI:7716503

• Allelic Composition: 3425401B19Rik^em1Liyu/3425401B19Rik^em1Liyu
• Genetic Background: involves: C57BL/6J

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:350467 )

• fewer than the expected number of mice are seen at weaning

• no mice with noncompaction are seen at 1 and 3 weeks after birth, suggesting that mice with noncompaction hearts are lethal

• starting from 3 weeks of age, mice show no increased mortality through 11 months of age

growth/size/body

enlarged heart ( J:350467 )

• 1 of 12 embryos show larger heart size and hypertrophy

• 2 of 13 mice at 1 week and 1 of 10 mice at 3 weeks of age exhibit hearts with larger size and hypertrophy

• hearts are larger at 4 and 8 months of age

• treatment with omecamtiv mecarbil reduces heart size

cardiac hypertrophy ( J:350467 )

• 1 of 12 embryos show larger heart size and hypertrophy

• 2 of 13 mice at 1 week and 1 of 10 mice at 3 weeks of age exhibit hearts with larger size and hypertrophy

cardiovascular system

abnormal heart morphology ( J:350467 )

• about half of hearts show variable phenotypes such as smaller size and noncompaction, normal size and noncompaction or larger size and hypertrophy

increased myocardial fiber size ( J:350467 )

• cross-sectional area of cardiomyocytes is greater at 4 and 8 months of age

• mice treated with omecamtiv mecarbil exhibit reduced cross-sectional area of cardiomyocyte

myocardial hypertrabeculation ( J:350467 )

• 2 of 12 embryos show smaller heart size and noncompaction

• 3 of 12 embryos show normal size and noncompaction

• no mice with noncompaction are seen at 1 and 3 weeks after birth, suggesting that mice with noncompaction hearts are lethal

enlarged heart ( J:350467 )

• 1 of 12 embryos show larger heart size and hypertrophy

• 2 of 13 mice at 1 week and 1 of 10 mice at 3 weeks of age exhibit hearts with larger size and hypertrophy

• hearts are larger at 4 and 8 months of age

• treatment with omecamtiv mecarbil reduces heart size

cardiac hypertrophy ( J:350467 )

• 1 of 12 embryos show larger heart size and hypertrophy

• 2 of 13 mice at 1 week and 1 of 10 mice at 3 weeks of age exhibit hearts with larger size and hypertrophy

small heart ( J:350467 )

• 2 of 12 embryos show smaller heart size and noncompaction

decreased heart weight ( J:350467 )

• mean heart weight is decreased at 4 months, but no difference is seen at 8 months

thin ventricular wall ( J:350467 )

• hearts with ventricular noncompaction phenotype have reduced ventricular wall thickness and increased trabecular area

cardiac fibrosis ( J:350467 )

• cardiac fibrosis is seen by 8 months of age, but not 4 months of age

dilated heart ( J:350467 )

• dilation of heart is seen at 4 and 8 months of age

dilated heart left ventricle ( J:350467 )

• degree of left ventricular dilatation worsens with age

dilated cardiomyopathy ( J:350467 )

• progression of cardiomyopathy with time

decreased cardiac stroke volume ( J:350467 )

• in mice at 4 and 8 months of age

decreased cardiac muscle contractility ( J:350467 )

• mice show lower ejection fraction and fractional shortening at 4 and 8 months of age

• mean ejection fraction of older (53-63-week-old mice) is 39%, while it is 58% at 8 months and mean fractional shortening of older mice is 19%, while it is 27% at 8 months

abnormal heart echocardiography feature ( J:350467 )

• echocardiograms show lower heart rate at 8 months of age, lower ejection fraction and fractional shortening, reduced stroke volume, increased left ventricular internal diameter (LVID) and left ventricular volume (LVVOL), and decreased left ventricular posterior wall thickness (LVPW) at end systole at 4 and 8 months of age and LVIDs and LVVOLs are further decreased with age

• LVID and LVVOL show a trend to being higher at end diastole, indicating that contraction impairments are more serious that relaxation impairments

• 12-week-old mice treated with omecamtiv mecarbil, a myosin activator, show improvement of ejection fraction and fractional shortening, reduction of LVID and LVVOL, and increased LVPW at end systole

decreased heart rate ( J:350467 )

• lower heart rate at 8 months of age, but not at 4 months

abnormal myocardial fiber physiology ( J:350467 )

• dramatical reduction in proliferation of the cardiomyocytes in the compact layer

• primary isolated cardiomyocytes show reduced shortening and reduced contraction and relaxation speeds

• however, no difference in time-to-peak, time-to-50% peak, or time-to-50% relaxation are seen

muscle

increased myocardial fiber size ( J:350467 )

• cross-sectional area of cardiomyocytes is greater at 4 and 8 months of age

• mice treated with omecamtiv mecarbil exhibit reduced cross-sectional area of cardiomyocyte

myocardial hypertrabeculation ( J:350467 )

• 2 of 12 embryos show smaller heart size and noncompaction

• 3 of 12 embryos show normal size and noncompaction

• no mice with noncompaction are seen at 1 and 3 weeks after birth, suggesting that mice with noncompaction hearts are lethal

dilated cardiomyopathy ( J:350467 )

• progression of cardiomyopathy with time

decreased cardiac muscle contractility ( J:350467 )

• mice show lower ejection fraction and fractional shortening at 4 and 8 months of age

• mean ejection fraction of older (53-63-week-old mice) is 39%, while it is 58% at 8 months and mean fractional shortening of older mice is 19%, while it is 27% at 8 months

abnormal sarcomere morphology ( J:350467 )

• cardiomyocytes show slightly decreased sarcomere length

• however, the arrangement of sarcomeres does not show obvious disorder

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:350467