Analysis Tools
mortality/aging
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• a decrease in fraction of viable mutants is first seen at E16.5, with few surviving after birth
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• only 3% of the expected 25% of mice are seen at weaning and mice rarely survive to adulthood
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cardiovascular system
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• E16.5 aortic valves lack the typical extended aortic sinuses seen in wild-type littermates
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• coronary artery network is reduced in rare viable P0 pups
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• mutants have dilated coronary veins at P0
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• hearts from rare viable P0 pups have a thickened compact myocardium
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• the proximal outflow tract, but not the neural crest cell-populated distal outflow tract, cushion contains about half the normal number of mesenchymal cells at E10.5, less than 24 hours after endocardial-to-mesenchymal trasnformation onset
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• E14.5 mutants occasionally have a small membranous ventricular septal defect which usually resolves by E16.5 in surviving mutants
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• hearts from rare viable P0 pups are larger
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• the thinner hinge region that demarcates the boundary between the distal and basal regions of each cusp of both aortic and pulmonic valves is absent at E16.5
• semilunar valve defects first become apparent at E14.5 as a decreased length:width ratio of the forming cusps
• expression analysis at E16.5 shows mislocalized extracellular matrix indicating a loss of patterning of the semilunar valve cusps into distinct base and distal regions
• however, the mitral valve is normal
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• aortic valves of rare survivors have myxomatous characteristics, with extensive proteoglycan-rich material throughout the valve and intermittent and dispersed collagen deposits rather than the typical enrichment of collagen along the atrial side of the cusps
• however, little or no change in calcification of aortic valves in rare surviving mice is seen
• rare survivors exhibit aortic valve disease with thickened, misorganized and myxomatous cusps, and bicuspid arrangement formation usually arising from left coronary cusp-non-coronary cusp fusion, without calcification
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• E16.5 aortic valves lack the typical thin elongated cusps seen in wild-type littermates
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• 3 of 6 mutants exhibit bicuspid aortic valves: the bicuspid valve originates from a fusion between the left and non-coronary cusps, with residual individual cusp attachment points to the surrounding muscle
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• hearts from newborns have thickened aortic valves
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• the left and right cusps of the pulmonic valve have decreased length:width ratios, are increased in area, and have a modest increase in the number of interstitial cells per valve section at E16.5
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• hearts from newborns have thickened pulmonic valves
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• semilunar valve cusps are thickened and poorly elongated at E16.5
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growth/size/body
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• hearts from rare viable P0 pups are larger
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muscle
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• hearts from rare viable P0 pups have a thickened compact myocardium
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