Analysis Tools
cardiovascular system
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• increase of connective tissue in the myocardium in 1 year old mice
• most cells in the myocardium of 1 year old mice contain multiple, large, and fused lysosomes containing heterogeneous electron-dense material
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• cardiomyocytes exhibit about twice as many nuclei per mm3 than controls, resulting in a decrease in volume of cytoplasm per nucleus
• many nuclei of cardiomyocytes are pleomorphic
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• by 12 months of age, about 75% of hearts show slight to moderate enlargement, with 25% showing severe enlargement
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• moderate left ventricular hypertrophy, with an increase of left ventricular dimensions in 1 year old mice
• 4 of 14 mice exhibit a severe enlargement of the left ventricle at the end of systole and diastole, accompanied by a 1.5-fold higher mass of the left ventricle
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• from 6 months of age, the relative heart weights increase
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• patches of interstitial fibrosis in hearts are first seen at 4 months of age
• however, inflammatory cell infiltrates are not seen in hearts
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• the cardiac index, describing the amount of heart work needed to maintain sufficient blood perfusion of the body, is increased in mice with severe ventricular and atrial dilation
• the maximal and average pressure gradients at the aortic valve of mice with extremely dilated hearts are elevated 3- to 4-fold
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• reduction in contraction of interventricular septum and posteriolateral wall
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• fractional shortening is reduced in all mice (left ventricular contraction), without further contraction reduction in mice with extreme ventricular enlargement
• the diameter and volume of the left ventricle at maximal contraction (the end of systole) is enhanced in all mice
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• all mice show increased left ventricular end-systolic diameter while mice with severely enlarged hearts exhibit increased left ventricular end-systolic diameter, end-diastolic volume, left ventricular end-diastolic diameter, left ventricle mass, left atrium diameter, maximum velocity of flow in the pw-doppler over aortic valve, maximum aortic pressure gradient, average aortic pressure gradient, and cardiac index
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• 4 of 14 mice show regurgitation at the mitral and aortic valves indicates valve insufficiencies in dilated hearts
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• 4 of 14 mice show regurgitation at the mitral and aortic valves indicates valve insufficiencies in dilated hearts
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• one mouse exhibits monomorphic ventricular extrabeats
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• 3 of 14 mice exhibit supraventricular tachycardia
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• one mouse exhibits atrioventricular block
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• the interval between the R- and T-waves of the ECG that reports activation and repolarization time of the ventricle is prolonged, with a flat and wide T-wave morphology
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• mice show higher R-wave voltages in standard limb lead II as an electrocardiographic sign of left ventricular hypertrophy
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• flat and wide T-wave morphology
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embryo
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• at E8.0, the extraembryonic yolk sac is more opaque and displays wrinkles and an uneven bulged surface, unlike the translucent control yolk sac tissue which shows a relatively smooth surface
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• at E8.0, the extraembryonic visceral endoderm shows wrinkled morphology, thickening of the visceral endoderm cell layer, and increased number and size of vesicular structures
• visceral endoderm cells are significantly enlarged and filled with large vesicular structures staining positive for glycoproteins in periodic acid-Schiff staining as well as for the lysosomal marker LAMP-1, indicating that accumulating vesicles are lysosomes
• however, early development of the epiblast appears normal
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integument
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• mice exhibit increased keratinocyte proliferation in the basal layer of back skin epidermis, as shown by Ki67 staining
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• mice exhibit epidermal hyperplasia with numerous proliferating cells
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mortality/aging
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• pups have a mortality rate of 15% compared to 6% for wild-type mice
• however, mortality rate of adults is not increased in mice up to 12 months of age
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muscle
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• increase of connective tissue in the myocardium in 1 year old mice
• most cells in the myocardium of 1 year old mice contain multiple, large, and fused lysosomes containing heterogeneous electron-dense material
|
|
• cardiomyocytes exhibit about twice as many nuclei per mm3 than controls, resulting in a decrease in volume of cytoplasm per nucleus
• many nuclei of cardiomyocytes are pleomorphic
|
|
• moderate left ventricular hypertrophy, with an increase of left ventricular dimensions in 1 year old mice
• 4 of 14 mice exhibit a severe enlargement of the left ventricle at the end of systole and diastole, accompanied by a 1.5-fold higher mass of the left ventricle
|
|
• reduction in contraction of interventricular septum and posteriolateral wall
|
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• fractional shortening is reduced in all mice (left ventricular contraction), without further contraction reduction in mice with extreme ventricular enlargement
• the diameter and volume of the left ventricle at maximal contraction (the end of systole) is enhanced in all mice
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immune system
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• at 8 weeks of age, mice exhibit a significantly decreased CD4+ T cell number in spleen relative to wild-type controls (4.2% versus 15.4%, respectively)
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cellular
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• patches of interstitial fibrosis in hearts are first seen at 4 months of age
• however, inflammatory cell infiltrates are not seen in hearts
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• at E8.0, embryos show a severe lysosomal storage phenotype in the visceral endoderm of the extraembryonic yolk sac
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• mice exhibit increased keratinocyte proliferation in the basal layer of back skin epidermis, as shown by Ki67 staining
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hematopoietic system
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• at 8 weeks of age, mice exhibit a significantly decreased CD4+ T cell number in spleen relative to wild-type controls (4.2% versus 15.4%, respectively)
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growth/size/body
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• by 12 months of age, about 75% of hearts show slight to moderate enlargement, with 25% showing severe enlargement
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• moderate left ventricular hypertrophy, with an increase of left ventricular dimensions in 1 year old mice
• 4 of 14 mice exhibit a severe enlargement of the left ventricle at the end of systole and diastole, accompanied by a 1.5-fold higher mass of the left ventricle
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• from 6 months of age, the relative heart weights increase
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| dilated cardiomyopathy | DOID:12930 |
OMIM:PS115200 |
J:76333 | |
