Phenotypes associated with this allele

• Allele Symbol: Des^tm1Cap
• Allele Name: targeted mutation 1, Yassemi Capetanaki
• Allele ID: MGI:2178321
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Des^tm1Cap/Des^tm1Cap	involves: 129S7/SvEvBrd	MGI:3773060
hm2	Des^tm1Cap/Des^tm1Cap	involves: 129S7/SvEvBrd * C57BL/6	MGI:2178322
cx3	Des^tm1Cap/Des^tm1Cap Tg(Bcl2)ACap/Tg(Bcl2)ACap	involves: 129S7/SvEvBrd * C57BL/6	MGI:3036355
cx4	Des^tm1Cap/Des^tm1Cap Tg(Bcl2)BCap/Tg(Bcl2)BCap	involves: 129S7/SvEvBrd * C57BL/6	MGI:3036356

Genotype
MGI:3773060

hm1

• Allelic Composition: Des^tm1Cap/Des^tm1Cap
• Genetic Background: involves: 129S7/SvEvBrd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Cardiac fibrosis and calcification seen in Des^tm1Cap/Des^tm1Cap mice is reduced in Des^tm1Cap/Des^tm1Cap Tg(Bcl2)ACap/Tg(Bcl2)ACap and Des^tm1Cap/Des^tm1Cap Tg(Bcl2)BCap/Tg(Bcl2)BCap mice

cardiovascular system

abnormal heart morphology ( J:88267 )

abnormal myocardial fiber morphology ( J:88267 )

• cardiomyocytes show disrupted contractile apparatus and numerous mitochondrial abnormalities, including loss of positioning, proliferation, clumping, and formation of cleared areas around mitochondria, and individual mitochondria appear swollen and misshapen

cardiac hypertrophy ( J:88267 )

• cardiac hypertrophy occurs in response to cardiac damage, with significant increase in heart size and distortion of the ventricles

cardiac fibrosis ( J:88267 )

dystrophic cardiac calcinosis ( J:88267 )

• fibrosis associated with calcium deposits is found throughout the left ventricle

abnormal cardiovascular system physiology ( J:88267 )

dilated cardiomyopathy ( J:88267 )

decreased heart ventricle muscle contractility ( J:88267 )

• impaired systolic function, showing decreased peak aortic velocity and mean acceleration

abnormal myocardial fiber physiology ( J:88267 )

• cardiomyocyte mitochondria exhibit increased sensitivity to calcium induced swelling

muscle

abnormal myocardial fiber morphology ( J:88267 )

• cardiomyocytes show disrupted contractile apparatus and numerous mitochondrial abnormalities, including loss of positioning, proliferation, clumping, and formation of cleared areas around mitochondria, and individual mitochondria appear swollen and misshapen

dilated cardiomyopathy ( J:88267 )

decreased heart ventricle muscle contractility ( J:88267 )

• impaired systolic function, showing decreased peak aortic velocity and mean acceleration

growth/size/body

cardiac hypertrophy ( J:88267 )

• cardiac hypertrophy occurs in response to cardiac damage, with significant increase in heart size and distortion of the ventricles

Genotype
MGI:2178322

hm2

• Allelic Composition: Des^tm1Cap/Des^tm1Cap
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

Myocardium degeneration and calcification in Des^tm1Cap/Des^tm1Cap mice

mortality/aging

premature death ( J:59831 )

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

cardiovascular system

abnormal myocardium layer morphology ( J:35123 )

abnormal myocardial fiber morphology ( J:35123 , J:59831 )

• 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)

disorganized myocardium ( J:35123 , J:59831 )

• loss of lateral alignment (J:35123)

• areas of disorganized and ragged myocytes, as commonly observed in hypertrophic myocardium (J:59831)

thin myocardium ( J:59831 )

• moderate to severe thinning of myocardial wall after sudden death

enlarged heart ( J:59831 )

• 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

cardiac hypertrophy ( J:59831 )

• 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

dilated heart left ventricle ( J:59831 )

• 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

dilated heart right ventricle ( J:59831 )

• 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

cardiac interstitial fibrosis ( J:35123 )

dystrophic cardiac calcinosis ( J:35123 , J:59831 )

• 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)

decreased heart ventricle muscle contractility ( 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

abnormal cardiac muscle relaxation ( J:59831 )

• enhanced diastolic function at 3 months of age (increased ratios of E/A peak velocities and areas), no longer evident after 13 months

cardiomyopathy ( J:35123 )

• 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

congestive heart failure ( J:59831 )

muscle

abnormal myocardium layer morphology ( J:35123 )

abnormal myocardial fiber morphology ( J:35123 , J:59831 )

• 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)

disorganized myocardium ( J:35123 , J:59831 )

• loss of lateral alignment (J:35123)

• areas of disorganized and ragged myocytes, as commonly observed in hypertrophic myocardium (J:59831)

thin myocardium ( J:59831 )

• moderate to severe thinning of myocardial wall after sudden death

decreased heart ventricle muscle contractility ( 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

abnormal cardiac muscle relaxation ( J:59831 )

• enhanced diastolic function at 3 months of age (increased ratios of E/A peak velocities and areas), no longer evident after 13 months

cardiomyopathy ( J:35123 )

• 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

abnormal skeletal muscle morphology ( J:35123 )

• 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)

abnormal smooth muscle morphology ( J:35123 )

• defects similar to those observed in striated muscle, but less severe

muscle degeneration ( J:35123 )

• degeneration of striated muscle

• more severe in cardiac muscle

behavior/neurological

lethargy ( J:35123 )

• noted by 2 weeks of age

impaired exercise endurance ( J:59831 )

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

homeostasis/metabolism

impaired exercise endurance ( J:59831 )

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

growth/size/body

enlarged heart ( J:59831 )

• 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

cardiac hypertrophy ( J:59831 )

• 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

cellular

cardiac interstitial fibrosis ( J:35123 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1I		DOID:0110431	OMIM:604765	J:35123
myofibrillar myopathy 1		DOID:0080092	OMIM:601419	J:35123

Genotype
MGI:3036355

cx3

• Allelic Composition: Des^tm1Cap/Des^tm1Cap; Tg(Bcl2)ACap/Tg(Bcl2)ACap
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

Cardiac fibrosis and calcification seen in Des^tm1Cap/Des^tm1Cap mice is reduced in Des^tm1Cap/Des^tm1Cap Tg(Bcl2)ACap/Tg(Bcl2)ACap and Des^tm1Cap/Des^tm1Cap Tg(Bcl2)BCap/Tg(Bcl2)BCap mice

cardiovascular system

cardiovascular system phenotype ( J:88267 )

N • the progressive calcification and degeneration observed in Des^tm1Cap homozygotes is ameliorated

cardiac interstitial fibrosis ( J:88267 )

• some fibrosis is observed, althought there are fewer and smaller fibrotic lesions than in Des^tm1Cap homozygotes

• more fibrosis than with similar mice carrying the Tg(Bcl2)BCap, which overexpresses higher levels of BCL2

dystrophic cardiac calcinosis ( J:88267 )

• some calcification is observed, although much less than in Des^tm1Cap homozygotes

• more calcification than with similar mice carrying the Tg(Bcl2)BCap, which overexpresses higher levels of BCL2

cellular

cardiac interstitial fibrosis ( J:88267 )

• some fibrosis is observed, althought there are fewer and smaller fibrotic lesions than in Des^tm1Cap homozygotes

• more fibrosis than with similar mice carrying the Tg(Bcl2)BCap, which overexpresses higher levels of BCL2

Genotype
MGI:3036356

cx4

• Allelic Composition: Des^tm1Cap/Des^tm1Cap; Tg(Bcl2)BCap/Tg(Bcl2)BCap
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

Cardiac fibrosis and calcification seen in Des^tm1Cap/Des^tm1Cap mice is reduced in Des^tm1Cap/Des^tm1Cap Tg(Bcl2)ACap/Tg(Bcl2)ACap and Des^tm1Cap/Des^tm1Cap Tg(Bcl2)BCap/Tg(Bcl2)BCap mice

cardiovascular system

cardiovascular system phenotype ( J:88267 )

N • the progressive calcification and degeneration observed in Des^tm1Cap homozygotes is ameliorated

abnormal myocardial fiber morphology ( J:88267 )

• although cadiomyocytes show a significant improvement from the damage seen in Des^tm1Cap homozygotes, some cardiomyocytes exhibit a loss of mitochondria alignment

cardiac interstitial fibrosis ( J:88267 )

• some fibrosis is observed, although there are fewer and smaller fibrotic lesions than in both Des^tm1Cap homozygotes and Des^tm1Cap homozygotes carrying Tg(Bcl2)ACap

dystrophic cardiac calcinosis ( J:88267 )

• some calcification is observed, althogh less than in both Des^tm1Cap homozygotes and Des^tm1Cap homozygotes carrying Tg(Bcl2)ACap

muscle

abnormal myocardial fiber morphology ( J:88267 )

• although cadiomyocytes show a significant improvement from the damage seen in Des^tm1Cap homozygotes, some cardiomyocytes exhibit a loss of mitochondria alignment

cellular

cardiac interstitial fibrosis ( J:88267 )

• some fibrosis is observed, although there are fewer and smaller fibrotic lesions than in both Des^tm1Cap homozygotes and Des^tm1Cap homozygotes carrying Tg(Bcl2)ACap