Analysis Tools
mortality/aging
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• morbidity rate at 2 to 7 months of age is 57.1% in mice that survive the postnatal period
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• most homozygotes die within the first 10 days after birth as a result of congestive heart failure
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cardiovascular system
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• at P5, homozygotes display congested livers
• however, bile ducts remain normal
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• at P5, homozygotes exhibit pulmonary congestion
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• fibrosis in the myocardium that worsens with age in surviving mice
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• at P5, mutant cardiomyocytes contain fewer, disorganized myofibrils, vacuolized and aberrantly shaped mitochondria, and numerous glycogen particles in the absence of myocyte hypertrophy or cardiomyopathy
(J:97120)
• cardiomyocytes show slightly thickened Z-discs and higher numbers of mitochondria and golgi bodies
(J:216895)
• cardiomyocyte degeneration with age
(J:216895)
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• width of myocardial cells in the ventricles are larger than in wild-type mice, becoming more prominent with age
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• at P5, homozygotes display dysplastic mitral valves relative to heterozygous mutant mice
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• at P5, homozygotes display dysplastic tricuspid valves relative to heterozygous mutant mice
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• at P5, the orifice of the mutant tricuspid valve is significantly smaller than that of the mitral valve
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• at P5, homozygotes exhibit a histologically obvious secundum atrial septal defect
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• at P5, both the left and right atria are enlarged
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• at P5, homozygotes exhibit thickening of the endocardium of the left atrium and left ventricle, with more elastin fibers and collagen fibers relative to heterozygous mutant mice
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• at P5, pulsed-wave Doppler echocardiograms exhibit high-velocity, broad, and upward waveforms during systole, indicating flow through a VSD; histology confirms the presence of a perimembranous VSD
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• at P5, the mutant heart occupies almost the entire thoracic cavity; a normal d-ventricular loop is observed
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• at P5, homozygotes show a significantly increased ratio of heart weight to body weight
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• sclerotic degeneration, including thickening, fibrosis and accumulation of glycosaminoglycans and reduced collagen-I, but not calcification, develops in the semilunar valves after birth and is seen in mutants that survive the postnatal period
(J:216895)
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• at P5, the mutant aortic valves have 3 leaflets, as expected; however, these leaflets appear relatively dysplastic
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• ratio of mice with aortic stenosis and regurgitation increase to 58.8% until more than 12 months of age
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• at P5, the mutant pulmonary valves have 3 leaflets, as expected; however, these leaflets appear relatively dysplastic
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• thickening develops after birth
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• thickening develops after birth
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• thickening develops after birth
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• at P5, homozygotes exhibit a significantly dilated left ventricular chamber
(J:97120)
• homozygous mutant LV internal dimensions at end-diastole and end-systole are larger than those in heterozygous mice
(J:97120)
• left ventricle internal dimension at systole and diastole is higher than in wild-type mice at 12 months of age
(J:216895)
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• 1 month old mice with aortic valve stenosis and regurgitation show severe thickening with fibrosis in the pulmonary and aortic valve leaflets, whereas mice without stenosis/regurgitation show slight thickening but not fibrosis in the aortic valve leaflets
• fibrosis is seen in border regions of the pulmonary and aortic valves of 2-3 month old mice, however calcification is rarely seen
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• at P5, homozygotes exhibit a significantly reduced fractional shortening of the left ventricle relative to heterozygous mutant mice (~38% vs ~50%, respectively), indicating impaired LV systolic function
(J:97120)
• in contrast, LV diastolic function remains unaffected, as shown by a normal E wave/A wave ratio, and aortic and pulmonary outflow tracts display normal waveform patterns
(J:97120)
• left ventricular fractional shortening is reduced (less than 23%) in about 41% of 12 month old mutants, indicating a decrease in left ventricle systolic function
(J:216895)
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• at P5, homozygotes exhibit AV valve regurgitation caused by dysplastic AV valves
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• at P5, transthoracic echocardiography indicates severe mitral valve regurgitation, with downward regurgitant jets noted at the mitral orifice during systole
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• at P5, transthoracic echocardiography indicates tricuspid valve regurgitation, with waveforms in the downward direction noted at the tricuspid orifice during systole
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• during diastole, abnormal downward and wide waveforms are seen at the aortic valve indicating regurgitation
• ratio of mice with aortic stenosis and regurgitation increase to 58.8% until more than 12 months of age
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• homozygotes exhibit a 15% reduction in heart rate relative to heterozygous mutant mice (312 31 vs 368 12, respectively)
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• most homozygotes die as a result of congestive heart failure
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growth/size/body
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• at P5, the mutant heart occupies almost the entire thoracic cavity; a normal d-ventricular loop is observed
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• at P5, homozygotes show a significantly increased ratio of heart weight to body weight
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• at P5, most homozygotes exhibit growth retardation relative to wild-type mice
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• at P5, homozygotes show a significantly increased ratio of lung weight to body weight
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respiratory system
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• at P5, homozygotes exhibit pulmonary congestion
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• at P5, homozygotes show a significantly increased ratio of lung weight to body weight
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• at P5, homozygotes exhibit pulmonary edema
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• at P5, homozygotes exhibit collapse of some alveoli
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• authors propose that pulmonary congestion and alveolar collapse ultimately cause heart failure and dyspnea leading to death
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muscle
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• fibrosis in the myocardium that worsens with age in surviving mice
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• at P5, mutant cardiomyocytes contain fewer, disorganized myofibrils, vacuolized and aberrantly shaped mitochondria, and numerous glycogen particles in the absence of myocyte hypertrophy or cardiomyopathy
(J:97120)
• cardiomyocytes show slightly thickened Z-discs and higher numbers of mitochondria and golgi bodies
(J:216895)
• cardiomyocyte degeneration with age
(J:216895)
|
|
• width of myocardial cells in the ventricles are larger than in wild-type mice, becoming more prominent with age
|
|
• at P5, homozygotes exhibit a significantly reduced fractional shortening of the left ventricle relative to heterozygous mutant mice (~38% vs ~50%, respectively), indicating impaired LV systolic function
(J:97120)
• in contrast, LV diastolic function remains unaffected, as shown by a normal E wave/A wave ratio, and aortic and pulmonary outflow tracts display normal waveform patterns
(J:97120)
• left ventricular fractional shortening is reduced (less than 23%) in about 41% of 12 month old mutants, indicating a decrease in left ventricle systolic function
(J:216895)
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• cardiomyocytes show slightly thickened Z-discs
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homeostasis/metabolism
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• at P5, homozygotes exhibit pulmonary edema
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liver/biliary system
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• at P5, homozygotes display congested livers
• however, bile ducts remain normal
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| aortic valve disease | DOID:62 | J:216895 | ||
