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

cellular

abnormal myocardial fiber mitochondrial morphology ( J:88267 )

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

cardiovascular system

abnormal heart morphology ( J:88267 )

abnormal myocardial fiber morphology ( J:88267 )

• cardiomyocytes show disrupted contractile apparatus

abnormal myocardial fiber mitochondrial morphology ( J:88267 )

• 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

abnormal myocardial fiber mitochondrial morphology ( J:88267 )

• 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 )

• loss of myocardial fiber tension

• interstitial fibrosis and necrosis

• detachment of fibers from the sarcolemma

abnormal myocardial fiber mitochondrial morphology ( J:35123 )

• disorganized mitochondria

increased myocardial fiber size ( J:59831 )

• a 24% increase in average cell volume of ventricular myocytes at 7 months, with no changes in cell length or profile area

disorganized myocardium ( J:59831 , J:35123 )

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

• loss of lateral alignment (J:35123)

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:59831 , 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)

• progressive calcification and degeneration, particularly of the left ventricle, evident by 3 weeks of age (J:35123)

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 )

• loss of myocardial fiber tension

• interstitial fibrosis and necrosis

• detachment of fibers from the sarcolemma

abnormal myocardial fiber mitochondrial morphology ( J:35123 )

• disorganized mitochondria

increased myocardial fiber size ( J:59831 )

• a 24% increase in average cell volume of ventricular myocytes at 7 months, with no changes in cell length or profile area

disorganized myocardium ( J:59831 , J:35123 )

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

• loss of lateral alignment (J:35123)

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

abnormal myocardial fiber mitochondrial morphology ( J:35123 )

• disorganized mitochondria

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