Analysis Tools
mortality/aging
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• about 25% of live-born homozygotes with normal cardiac structure die shortly after birth or within the first days of life due to defective lung maturation
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• about 25% of live-born homozygotes with normal cardiac structure die shortly after birth or within the first days of life due to defective lung maturation
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• about 50% of homozygotes develop embryonic heart failure and die between E10.5 and E12.5
• homozygotes that survive to birth appear healthy and fertile up to 6 months of age, with no evidence of myocardial dysfunction
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cardiovascular system
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• at E10.5, ~50% of homozygotes exhibit microperforations of the myocardium
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• at E10.5, ~50% of homozygotes exhibit a poorly developed, thinned compact zone
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• at E10.5, ~50% of homozygotes exhibit a thinned myocardial wall
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• at E10.5, ~50% of homozygotes exhibit gross pericardial effusions, often containing sero-sanguinous exudates
• notably, homozygotes without pericardial effusions display histogically normal hearts
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• mutant lungs display hemorrhage in distal airways
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• ECG recordings indicate that 50% of homozygotes display a right axis deviation that is not observed in wild-type littermates
• however, resting heart rates and baseline PR-intervals remain normal in the absence of spontaneous arrhythmias
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• intracardiac electrophysiological data indicate HV-interval prolongation, suggesting a distal infrahisian conduction delay
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• surface ECG data (including sedated 6-lead ECG and conscious telemetry ECG) indicate P-wave widening
• intracardiac electrophysiological data indicate a prolonged atrial effective refractory period (AERP)
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• surface ECG data (including sedated 6-lead ECG and conscious telemetry ECG) indicate QT-interval prolongation
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• at 10-14 weeks of age, homozygotes display conduction defects below the atrioventricular node (AVN), associated with decreased expression of connexin40; however, the size and integrity of the AVN and His-bundle appear unaffected
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• surface ECG data (including sedated 6-lead ECG and conscious telemetry ECG) indicate QRS-complex widening
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homeostasis/metabolism
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• at E10.5, ~50% of homozygotes exhibit gross pericardial effusions, often containing sero-sanguinous exudates
• notably, homozygotes without pericardial effusions display histogically normal hearts
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respiratory system
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• mutant lungs display hemorrhage in distal airways
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• 4 of 5 homozygotes that die early in postnatal life display defective lung maturation
• affected mutants display a thickened interairway mesenchyme and reduced alveolar septal development
• at P21, half (2 of 4) surviving adults show a ~50% decrease in total cell counts from bronchoalveolar lavage, suggesting impaired mesenchymal development
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• alveolar septal development is reduced
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• at P21, half (2 of 4) surviving adults show a ~50% decrease in total cell counts from bronchoalveolar lavage, suggesting impaired mesenchymal development
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• the mesenchyme of postnatal mutant lungs is thicker than that of wild-type lungs
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• defective type 2 pneumocyte maturation
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• at P21, half (2 of 4) surviving adults display a 17-19% decrease in lung function, as measured by tidal volume
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• dramatic increases in secreted surfactant are observed in mutant airways
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muscle
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• at E10.5, ~50% of homozygotes exhibit microperforations of the myocardium
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• at E10.5, ~50% of homozygotes exhibit a poorly developed, thinned compact zone
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• at E10.5, ~50% of homozygotes exhibit a thinned myocardial wall
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