mortality/aging
• those that survive gestation (about 44%) die within the first two weeks after birth
|
• death after E13.5, incomplete penetrance (~56%), remainder die postnatally
|
cardiovascular system
• 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
|
• at E17-P1, exhibit signs of myofibril degeneration
|
• 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
|
• cardiomyocyte disorganization, myofilament disarray
|
• 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
|
• at E17 and P1, mutant hearts are significantly enlarged
|
growth/size/body
• at E17 and P1, mutant hearts are significantly enlarged
|
• smaller than littermates, incomplete penetrance
|
muscle
• 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
|
• at E17-P1, exhibit signs of myofibril degeneration
|
• cardiomyocyte disorganization, myofilament disarray
|
• 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
|
• 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
|
• hearts show variable but extensive loss of thin filaments within the sarcomeres
|
• at P1, homozygotes display cardiomyocyte degeneration, as shown by loss of myofibrils, cytoplasmic condensation, condensed chromatin, and myofilament size and shape irregularities
|
cellular
• 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
|