mortality/aging
• about half of mutants die between E16.5 and P0
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cardiovascular system
• E16.5 vasculature is characterized by a lower surface area to volume ratio, suggesting that proper capillary network formation is compromised
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• capillary density is reduced in E14.5 to E16.5 hearts
• the number of capillary structures in a given heart volume is reduced at E16.5
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• mild, but significant, reduction of the radial lengths of the capillary network in retinas at P2 and P6
• however, filopodia and branching-point densities are not affected in the retina
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• persistent directional migration of primary mouse cardiac endothelial cells (MCECs) is reduced and capillary density is reduced in E14.5-E16.5 hearts, indicating abnormal microvascular angiogenesis
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• capillary density is reduced in E14.5 to E16.5 hearts, however hearts are normal at E12.5
• only about 5% of MCECs exhibit organized perinuclear actin fibers compared to about 60% of wild-type MCECs and colocalization of septin filaments and F-actin in the perinuclear region is reduced
• MCECs show a loss of the perinuclear septin patch and parallel actin fibers, and of organized phosphorylated myosin light chain staining in the perinuclear region
• however, MCECs from adult hearts show no defect in proliferation in vitro, attach to coverslips and are able to form adherens junctions, and exhibit similar centrosome/Golgi positioning after scratch wounding
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• ventricular walls of hearts are thinner at E15.5
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cellular
• in a heart explant model, mouse cardiac endothelial cells (MCECs) show a reduction in persistent directional migration and reduced migration speed
• MCECs exhibit a reduction in persistent directional migration during in vitro scratch wound-healing migration, however MCECs migrate faster than wild-type MCECs in two-dimensional assay
• in a heart explant model, sprouts formed by mutant hearts are shorter than in control explants
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growth/size/body
• mice that survive beyond P0 exhibit reduced body weight from birth to adulthood
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vision/eye
• however, filopodia and branching-point densities are not affected in the retina
• mild, but significant, reduction of the radial lengths of the capillary network in retinas at P2 and P6
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embryo
N |
• no obvious defects in the placenta
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hematopoietic system
N |
• no signs of anemia or liver discoloration are seen
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reproductive system
N |
• males and females are fertile
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