Analysis Tools
cardiovascular system
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• in mice that die in the first day and in all mice by 4 months
• pronounced sarcomere fragmentation and disorganization
• disrupted Z discs
• vacuolation of mitochondria and loss of cristae
• 2.5 fold increase in cardiomyocyte proliferation
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• in mice that die in the first day
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• ventricular septum is fenestrated and thinned about 25%
• hypocellularity of the wall of the ventricular septum near the apex of the heart in a subset of mutants at P1
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• all dKO mice that died at P1 exhibited large VSDs near the apex
• similar to, although more severe than, the trabecular (muscular) VSD in humans
• also observed VSDs near the atrioventricular valve at P1
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• free wall of the right ventricle is thinned to half the thickness of controls at E15.5
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• free wall of the right ventricle at E15.5
• free wall of both ventricles at E17.5 and in mice that survive to 5-6 months
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• at E15.5 and at E17.5
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• extensive by 4 months of age but no cardiomyocyte hypertrophy
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• at 5-6 months of age
• about half of 5-6 month old mice experience sudden death
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• at systole by 2-4 months of age
• impaired fractional shortening of the heart
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• increased left ventricular inner diameter at systole
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muscle
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• in mice that die in the first day and in all mice by 4 months
• pronounced sarcomere fragmentation and disorganization
• disrupted Z discs
• vacuolation of mitochondria and loss of cristae
• 2.5 fold increase in cardiomyocyte proliferation
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• at 5-6 months of age
• about half of 5-6 month old mice experience sudden death
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• at systole by 2-4 months of age
• impaired fractional shortening of the heart
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• increased left ventricular inner diameter at systole
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• at day 1
• at the apex and base of the interventricular septum
• near the atrioventricular valves
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mortality/aging
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• underrepresented at birth, and 50% of the remaining mice die within the first postnatal day
• ~24% of total dKO mice survived to adulthood
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• analysis of offspring from timed matings of heterozygous mutant mice revealed dKO mutant embryos between embryonic day 10.5 (E10.5) and E17.5 at a frequency slightly less than Mendelian with occasional dead dKO embryos
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homeostasis/metabolism
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• blood filled and containing thrombi in mice that die in the first day
• atrial thrombi in mice that survive to 5-6 months
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cellular
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• at day 1
• at the apex and base of the interventricular septum
• near the atrioventricular valves
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growth/size/body
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• in mice that die in the first day
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