mortality/aging
• mice are born alive but exhibit postnatal death around 3rd week of age and are all dead by 9th week
• males die sooner than females, around 6 weeks of age
• mice show signs of distress 1-2 days before death
|
growth/size/body
• at 25 days of age, both males and females show a significant increase in heart weight/body weight ratios relative to controls
|
• surviving males show a significant decrease in body weight at 4 and 5 weeks of age relative to controls
• in contrast, females show normal body weight up to 6 weeks of age
|
cardiovascular system
• at 25 days of age, the area and perimeter of the area between cardiac muscle fibers are increased relative to controls
• cardiac fibers show altered sarcomeres with irregular Z-discs and unidentifiable M-lines, disarrayed thin filaments, and distorted intercalated discs
|
• at 25 days of age, cardiac fibers display less convoluted intercalated discs (ICDs) with reduced electron-dense staining, indicating less ICD component proteins
• expression of two key ICD genes, beta-catenin and Connexin43 (components of fascia adherens and gap junctions, respectively) is reduced
|
• at 25 days of age, both males and females show a significant increase in heart weight/body weight ratios relative to controls
|
• at 25 days of age, all mice exhibit thin ventricular walls during both systolic and diastolic periods
|
• at 25 days of age, all mice exhibit dilated heart ventricular lumens
|
• at 25 days of age, mutant hearts display dilated cardiomyopathy defects with a significant increase in expression of the heart hypertrophy and heart failure biomarkers, atrial natriuretic factor (ANF) and
brain natriuretic peptide (BNP), before detection of heart failure
• however, no increase in cardiac fibrosis is observed
|
• at 25 days of age, mice display markedly reduced ejection fraction and fractional shortening values relative to controls
|
• at 25 days of age, mice display delayed electrical repolarization of the ventricles (as shown by lengthened QTc value), indicating ventricular arrhythmia
|
• at 25 days of age, mice display a lengthened corrected QT interval (QTc) value relative to controls
|
muscle
• at 25 days of age, the area and perimeter of the area between cardiac muscle fibers are increased relative to controls
• cardiac fibers show altered sarcomeres with irregular Z-discs and unidentifiable M-lines, disarrayed thin filaments, and distorted intercalated discs
|
• at 25 days of age, cardiac fibers display less convoluted intercalated discs (ICDs) with reduced electron-dense staining, indicating less ICD component proteins
• expression of two key ICD genes, beta-catenin and Connexin43 (components of fascia adherens and gap junctions, respectively) is reduced
|
• at 25 days of age, mutant hearts display dilated cardiomyopathy defects with a significant increase in expression of the heart hypertrophy and heart failure biomarkers, atrial natriuretic factor (ANF) and
brain natriuretic peptide (BNP), before detection of heart failure
• however, no increase in cardiac fibrosis is observed
|
• at 25 days of age, mice display markedly reduced ejection fraction and fractional shortening values relative to controls
|
• at 25 days of age, sarcomeres are shortened and disorganized in the myocardium
|
• at 25 days of age, M-lines are unrecognizable in the myocardium
|
• at 25 days of age, Z-discs are disorganized in the myocardium
|
behavior/neurological
trunk curl
(
J:233669
)
• mice exhibit curling up 1-2 days prior to death
|
• mice exhibit less movement 1-2 days prior to death
|
respiratory system
• mice exhibit dyspnea 1-2 days prior to death
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
dilated cardiomyopathy | DOID:12930 |
OMIM:PS115200 |
J:233669 |