Analysis Tools
mortality/aging
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• 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
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growth/size/body
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• 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
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• 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
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cardiovascular system
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• about half of hearts show variable phenotypes such as smaller size and noncompaction, normal size and noncompaction or larger size and hypertrophy
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• 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
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• 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
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• 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
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• 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
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small heart
(
J:350467
)
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• 2 of 12 embryos show smaller heart size and noncompaction
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• mean heart weight is decreased at 4 months, but no difference is seen at 8 months
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• hearts with ventricular noncompaction phenotype have reduced ventricular wall thickness and increased trabecular area
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• cardiac fibrosis is seen by 8 months of age, but not 4 months of age
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• dilation of heart is seen at 4 and 8 months of age
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• degree of left ventricular dilatation worsens with age
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• progression of cardiomyopathy with time
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• in mice at 4 and 8 months of age
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• 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
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• 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
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• lower heart rate at 8 months of age, but not at 4 months
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• 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
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muscle
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• 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
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• 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
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• progression of cardiomyopathy with time
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• 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
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• cardiomyocytes show slightly decreased sarcomere length
• however, the arrangement of sarcomeres does not show obvious disorder
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| dilated cardiomyopathy | DOID:12930 |
OMIM:PS115200 |
J:350467 | |
