Mouse Genome Informatics
hm
    Destm1Cap/Destm1Cap
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Myocardium degeneration and calcification in Destm1Cap/Destm1Cap mice

mortality/aging
• 6% of homozygotes die suddenly before reaching 1 year of age

cardiovascular system
• loss of myocardial fiber tension (J:35123)
• interstitial fibrosis and necrosis (J:35123)
• detachment of fibers from the sarcolemma (J:35123)
• disorganized mitochondria (J:35123)
• a 24% increase in average cell volume of ventricular myocytes at 7 months, with no changes in cell length or profile area (J:59831)
• loss of lateral alignment (J:35123)
• areas of disorganized and ragged myocytes, as commonly observed in hypertrophic myocardium (J:59831)
• moderate to severe thinning of myocardial wall after sudden death
• mild heart enlargement is frequently observed in the absence of stress
• severe heart enlargement is noted after sudden death or after exercise-induced stress
• prominent heart enlargement and ventricular dilation also observed in aging homozygotes
• a 20% increase in HW/BW ratio by 1 month of age or later
• concentric cellular hypertrophy of ventricular myocytes, with normal major diameters but a 30% increase in minor diameters at 7 months
• changes in expression pattern of hypertrophic markers associated with pressure overload hypertrophy at 1 and 6 months
• slight dilation of left ventricle in the absence of stress, with no severe changes in myocardial wall thickness
• severe dilation of the left ventricle after sudden death, with moderate to severe thinning of myocardial wall
• slight dilation of right ventricle in the absence of stress, with no severe changes in myocardial wall thickness
• severe dilation of the right ventricle after sudden death, with moderate to severe thinning of myocardial wall
• progressive calcification and degeneration, particularly of the left ventricle, evident by 3 weeks of age (J:35123)
• calcified lesions and areas of fibrous replacement of myocardial tissue as early as 1 week after birth; most prominent in the right ventricle and toward the inner and outer surfaces of the myocardium (J:59831)
• significantly impaired systolic function (reduced peak aortic flow velocity and average aortic acceleration) at 13-14 months of age, with a 20% reduction in peak aortic flow velocity evident at 3-13 months or later
• enhanced diastolic function at 3 months of age (increased ratios of E/A peak velocities and areas), no longer evident after 13 months
• progressive calcification and degeneration, particularly of the left ventricle, evident by 3 weeks of age
• lesions appeared to progress from the exterior of the myocardium inward

muscle
• loss of myocardial fiber tension (J:35123)
• interstitial fibrosis and necrosis (J:35123)
• detachment of fibers from the sarcolemma (J:35123)
• disorganized mitochondria (J:35123)
• a 24% increase in average cell volume of ventricular myocytes at 7 months, with no changes in cell length or profile area (J:59831)
• significantly impaired systolic function (reduced peak aortic flow velocity and average aortic acceleration) at 13-14 months of age, with a 20% reduction in peak aortic flow velocity evident at 3-13 months or later
• enhanced diastolic function at 3 months of age (increased ratios of E/A peak velocities and areas), no longer evident after 13 months
• progressive calcification and degeneration, particularly of the left ventricle, evident by 3 weeks of age
• lesions appeared to progress from the exterior of the myocardium inward
• similar abnormalities as observed in cardiac muscle, but to a lesser extent
• ragged, disorganized fibers with a loss of tension
• disorganized mitochondria
• increased severity of myofibril defects in muscles with high usage (e.g. tongue muscle)
• defects similar to those observed in striated muscle, but less severe
• degeneration of striated muscle
• more severe in cardiac muscle

behavior/neurological
• noted by 2 weeks of age
• 50% of homozygotes show impaired excercise capacity and die during swimming

homeostasis/metabolism
• 50% of homozygotes show impaired excercise capacity and die during swimming

Mouse Models of Human Disease
OMIM IDRef(s)
Cardiomyopathy, Dilated, 1I; CMD1I 604765 J:35123
Myopathy, Myofibrillar, 1; MFM1 601419 J:35123