Analysis Tools
mortality/aging
 |
• mice are born at expected Mendelian ratios with 77% surviving beyond 50 weeks of age
|
|
|
• 33% of mice die before 50 weeks of age and fewer than 5% show lethality between 1 week and 2 months of age with enlarged hearts
|
cardiovascular system
|
|
• hearts show an elevated number of abnormal mitochondria, including variable size, donut and onion-shaped mitochondria, and mitochondria with disorganized cristae
• mitochondrial size in the heart is reduced 50% and lengths are slightly increased, indicating elongated mitochondria
• hearts show a significant number of mitochondria devoid of normal cristae structures but with an increased inner membrane surface, forming large internal membrane stacks that fail to invaginate into tubular or fenestrated laminar cristae
|
|
|
• at 4 months of age, hearts of surviving mice show a more rounded shape compared to controls
|
|
|
• enlarged hearts are seen in the mice that show lethality between 1 week and 2 months of age
|
|
|
• width of ventricles is enlarged resulting in a decreased height/width ratio at 4 months of age
• however, no differences in ventricular weight to body weight or ventricular weight to tibia length ratios are seen at 2 or 4 months of age
|
|
|
• mice show dilated left ventricular chambers at 4 months of age, however no overtly enlarged hearts are seen at 4 months
• however, no differences in right ventricular chambers are seen
|
|
|
• majority of mice develop dilated cardiomyopathy at 4 months of age, with increased end-diastolic left ventricle internal diameter and end-systolic left ventricle internal diameter
• however, no arrhythmias are detected in mice at 2 weeks, 2 months, or 6 months of age and no increase in cardiac fibrosis or cardiomyocyte death is seen
|
|
|
• mice show reduced left ventricle fractional shortening at 4 and 6 months of age
|
|
|
• echocardiography shows decreased left ventricle systolic function, with reduced left ventricle fractional shortening, increased end-diastolic left ventricle internal diameter, and end-systolic left ventricle internal diameter
|
growth/size/body
|
|
• enlarged hearts are seen in the mice that show lethality between 1 week and 2 months of age
|
homeostasis/metabolism
|
|
• approximate 50% reduction in total cardiolipin levels in hearts at 2 and 4 months of age while levels of monolysocardiolipin and the further degradation product dilysocardiolipin are elevated resulting in monolysocardiolipin/cardiolipin ratios that are increased about 50-fold
• hearts shows an accumulation of cardiolipins with shorter or more saturated acyl groups and reduced levels of mature cardiolipin species with longer and more unsaturated acyl groups, including the most predominant form tetralinoleoyl-cardiolipin (72:8)
• levels of total phosphatidic acid and phosphatidylglycerol are increased in ventricular tissues
• accumulation of phosphatidylcholine and phosphatidylethanolamine species likely containing linoleic acid, such as phosphatidylcholine (36:2; likely phosphatidylcholine [18:0/18:2]) and phosphatidylethanolamine (36:2; likely phosphatidylethanol-amine [18:0/18:2]) in ventricular tissue
|
cellular
|
|
• hearts show mitochondria with disorganized cristae
|
|
|
• hearts show an elevated number of abnormal mitochondria, including donut and onion-shaped mitochondria, and mitochondria with disorganized cristae
|
|
|
• heart mitochondrial size is reduced 50% and lengths are slightly increased, indicating elongated mitochondria
|
|
|
• mitochondrial number is increased in myocardium
|
|
|
• mitochondrial respiration capacity is decreased in the heart, with heart mitochondria showing reduced state 3 and maximal respiratory rates for complex I substrates pyruvate/malate and palmitoyl carnitine/mmalate and complex II substrates succinate/rotenone
• however, enzymatic activities of each individual complex are not altered and no differences in lactate production is seen in hearts
|
|
|
• levels of reactive oxygen species (ROS) and superoxide are elevated in mitochondria from 2-month-old hearts
• however, no difference in mitochondrial membrane potential is seen indicating that the elevated levels of ROS and superoxide are due to reduced respiration capacity
|
|
|
• organization of high molecular weight respiratory chain super complexes is impaired in heart mitochondria; higher-order assemblies of complex I-containing and complex III-containing respiratory chain supercomplexes (RCS) are diminished in heart mitochondria while lower molecular weight oligomers of RCS containing complexes I and III2 and individual complexes I and III are increased
• complex IV-containing RCS are reduced and individual complex IV is increased
|
muscle
|
|
• majority of mice develop dilated cardiomyopathy at 4 months of age, with increased end-diastolic left ventricle internal diameter and end-systolic left ventricle internal diameter
• however, no arrhythmias are detected in mice at 2 weeks, 2 months, or 6 months of age and no increase in cardiac fibrosis or cardiomyocyte death is seen
|
|
|
• mice show reduced left ventricle fractional shortening at 4 and 6 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Barth syndrome | DOID:0050476 |
OMIM:302060 |
J:339058 | |
| cardiomyopathy | DOID:0050700 | J:339058 | ||
