Phenotypes associated with this allele

• Allele Symbol: Actc1^tm1Jll
• Allele Name: targeted mutation 1, James Lessard
• Allele ID: MGI:2180072
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Actc1^tm1Jll/Actc1^tm1Jll	involves: 129P2/OlaHsd * Black Swiss	MGI:2447434
cx2	Actc1^tm1Jll/Actc1^tm1Jll Tg(Myh6-Actg2)1Jll/0	involves: 129P2/OlaHsd * Black Swiss * FVB/N	MGI:3584000

Genotype
MGI:2447434

hm1

• Allelic Composition: Actc1^tm1Jll/Actc1^tm1Jll
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss

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

Myofibrillar disarray in newborn Actc1^tm1Jll/Actc1^tm1Jll hearts

mortality/aging

postnatal lethality, complete penetrance ( J:40165 )

• those that survive gestation (about 44%) die within the first two weeks after birth

lethality throughout fetal growth and development, incomplete penetrance ( J:40165 )

• death after E13.5, incomplete penetrance (~56%), remainder die postnatally

cardiovascular system

abnormal myocardial fiber morphology ( J:102007 )

• at E17-P1, homozygotes exhibit progressive nuclear changes accompanied by disorganization or loss of the myofibrils as well as other signs of degeneration; notably, the plasma membrane is often intact

myocardial fiber degeneration ( J:102007 )

• at E17-P1, exhibit signs of myofibril degeneration

disorganized myocardium ( J:102007 )

• at E17 and P1, cardiac muscle tissue appears underdeveloped with cells detached sideways from each other

• at P1, myofilaments are developmentally retarded, fail to organize into uniform bundles and occasionally resemble primitive, immature bundles

• at P1, fragmentation of cellular material and disorganization of the myofibrils, increased intercellular space, accumulation of glycogen granules, degraded myofilaments, some fibrosis, and cardiomyocyte hypertrophy with connective tissue replacement are observed

myocardial fiber disarray ( J:40165 )

• cardiomyocyte disorganization, myofilament disarray

delayed heart development ( J:102007 )

• at E12 and E14, cardiac development is normal but occasionally delayed

• however, no major differences in the developing anatomical structures or the proportion of apoptotic cells are observed

enlarged heart ( J:102007 )

• at E17 and P1, mutant hearts are significantly enlarged

growth/size/body

enlarged heart ( J:102007 )

• at E17 and P1, mutant hearts are significantly enlarged

decreased body size ( J:40165 )

• smaller than littermates, incomplete penetrance

muscle

abnormal myocardial fiber morphology ( J:102007 )

• at E17-P1, homozygotes exhibit progressive nuclear changes accompanied by disorganization or loss of the myofibrils as well as other signs of degeneration; notably, the plasma membrane is often intact

myocardial fiber degeneration ( J:102007 )

• at E17-P1, exhibit signs of myofibril degeneration

myocardial fiber disarray ( J:40165 )

• cardiomyocyte disorganization, myofilament disarray

disorganized myocardium ( J:102007 )

• at E17 and P1, cardiac muscle tissue appears underdeveloped with cells detached sideways from each other

• at P1, myofilaments are developmentally retarded, fail to organize into uniform bundles and occasionally resemble primitive, immature bundles

• at P1, fragmentation of cellular material and disorganization of the myofibrils, increased intercellular space, accumulation of glycogen granules, degraded myofilaments, some fibrosis, and cardiomyocyte hypertrophy with connective tissue replacement are observed

increased cardiomyocyte apoptosis ( J:102007 )

• at E17-P1, homozygotes display a progressive increase of cardiomyocyte apoptosis in the ventricular wall as well as a mild, focal, single-myocyte degeneration; apoptosis is less prominent in the atrial wall

• at P1, apoptosis in the ventricular wall is distributed in the compact wall and trabeculae as well as in the interventricular septum

abnormal sarcomere morphology ( J:40165 )

• hearts show variable but extensive loss of thin filaments within the sarcomeres

muscle degeneration ( J:102007 )

• at P1, homozygotes display cardiomyocyte degeneration, as shown by loss of myofibrils, cytoplasmic condensation, condensed chromatin, and myofilament size and shape irregularities

cellular

increased cardiomyocyte apoptosis ( J:102007 )

• at E17-P1, homozygotes display a progressive increase of cardiomyocyte apoptosis in the ventricular wall as well as a mild, focal, single-myocyte degeneration; apoptosis is less prominent in the atrial wall

• at P1, apoptosis in the ventricular wall is distributed in the compact wall and trabeculae as well as in the interventricular septum

Genotype
MGI:3584000

cx2

• Allelic Composition: Actc1^tm1Jll/Actc1^tm1Jll; Tg(Myh6-Actg2)1Jll/0
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss * FVB/N

Cardiac hypertrophy in Actc1^tm1Jll/Actc1^tm1Jll Tg(Myh6-Actg2)1Jll mice

cardiovascular system

enlarged heart ( J:40165 )

• enlarged, rounded hearts

heart left ventricle hypertrophy ( J:40165 )

• hypertrophy of left ventricular septum and free wall

• thickening of endothelium of the left ventricle with fibrous tissue

• myocyte hypertrophy

dilated heart right ventricle ( J:40165 )

• dilation of right ventricular free wall

cardiac fibrosis ( J:40165 )

• mild

decreased cardiac muscle contractility ( J:40165 , J:107848 )

• hypodynamic; maximal rates of contraction and relaxation are reduced to 40% of the values obtained for controls (J:40165)

• skinned fiber bundles from transgenic mouse hearts ectopically expressing enteric smooth muscle gamma-actin show no differences in maximum Ca²⁺ activated tension or maximum rate of tension redevelopment after a quick release and rapid restretch protocol (J:107848)

• however, transgenic fiber bundles exhibit a reduced sensitivity to Ca²⁺ tension and an increased economy of force development (~35% less ATP hydrolysis) relative to nontransgenic fiber bundles (J:107848)

• reduced sensitivity to Ca²⁺ tension coupled with slower cross-bridge cycling rates are likely to account for the slow rate of contraction noted in the intact heart (J:107848)

decreased heart ventricle muscle contractility ( J:40165 )

• significantly reduced rate of ventricular contraction and relaxation

abnormal cardiac muscle relaxation ( J:40165 )

• reduction in the rate of ventricular relaxation

decreased systemic arterial blood pressure ( J:40165 )

homeostasis/metabolism

abnormal cardiac thrombosis ( J:40165 )

• thrombi evident in left ventricular wall and occluding the highly dilated right atrium

muscle

heart left ventricle hypertrophy ( J:40165 )

• hypertrophy of left ventricular septum and free wall

• thickening of endothelium of the left ventricle with fibrous tissue

• myocyte hypertrophy

decreased cardiac muscle contractility ( J:40165 , J:107848 )

• hypodynamic; maximal rates of contraction and relaxation are reduced to 40% of the values obtained for controls (J:40165)

• skinned fiber bundles from transgenic mouse hearts ectopically expressing enteric smooth muscle gamma-actin show no differences in maximum Ca²⁺ activated tension or maximum rate of tension redevelopment after a quick release and rapid restretch protocol (J:107848)

• however, transgenic fiber bundles exhibit a reduced sensitivity to Ca²⁺ tension and an increased economy of force development (~35% less ATP hydrolysis) relative to nontransgenic fiber bundles (J:107848)

• reduced sensitivity to Ca²⁺ tension coupled with slower cross-bridge cycling rates are likely to account for the slow rate of contraction noted in the intact heart (J:107848)

decreased heart ventricle muscle contractility ( J:40165 )

• significantly reduced rate of ventricular contraction and relaxation

abnormal cardiac muscle relaxation ( J:40165 )

• reduction in the rate of ventricular relaxation

growth/size/body

enlarged heart ( J:40165 )

• enlarged, rounded hearts

heart left ventricle hypertrophy ( J:40165 )

• hypertrophy of left ventricular septum and free wall

• thickening of endothelium of the left ventricle with fibrous tissue

• myocyte hypertrophy