Analysis Tools
mortality/aging
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• by E11.5, homozygotes are obtained at a reduced Mendelian frequency; no live homozygotes are recovered at E14.5
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endocrine/exocrine glands
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• at E9.5, some homozygotes initiate thyroid gland formation; however, thyroid glands undergo degeneration such that no glands are present by E13.5
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liver/biliary system
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• at E9.5, homozygotes display severe defects in liver development
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absent liver
(
J:93580
)
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• no livers are identified at E13.5
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nervous system
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• at E9.5-E14.5, a subset of homozygotes exhibit anterior truncations of the brain/head with variability in the severity of the forebrain defect
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• variable forebrain truncations
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cardiovascular system
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• at E13.5, homozygotes exhibit disorganization of sprouting endothelial tubes and significantly dilated blood vessels
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• at E9.5-E10.0, homozygotes display only subtle vascular abnormalities such as disorganization of the developing cranial vasculature
• at E11.5, homozygotes show a striking profusion of small, ectopic vessels and disorganization of large vasculature throughout the whole embryo
• by E13.5, homozygotes display massive dilation of the internal jugular vein, intercostal vessels, and vessels in the septum transversum mesenchyme
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• at E11.5, all homozygotes exhibit reduced or delayed VSMC formation in the cranial vasculature, dorsal aorta, intersomitic and branchial vessels, although severity is variable
• notably, embryos with the most severe forebrain phenotype show complete absence of VSMCs in the cranial vessels at E11.5
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• at E13.5, the trabecular layer of the mutant myocardium appears thicker and more cellular than normal
• in severe cases, the mutant myocardium appears to be composed almost entirely of the trabecular layer
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• at E13.5, homozygotes exhibit an abnormally thin compact myocardial layer (only 2-3 cells thick) and cells are more closely packed together
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• epithelial-mesenchymal transformation is upregulated, partly due to a 2- to 3-fold elevation in cardiac Vegfa levels between E9.5 and E11.5
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• at E13.5, homozygotes show overabundance of endocardial cushion cells (ECCs) and cardiac jelly in both the AV cushion and the endocardial cushion that forms the right ventricular outflow tract
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• at E13.5, homozygotes show overabundance of endocardial cushion cells (ECCs) and cardiac jelly in both the AV cushion and the endocardial cushion that forms the right ventricular outflow tract
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• at E13.5, the abnormally large atrioventricular cushions fail to condense and thin normally
• endocardial cushion enlargement is due to a 75% reduction in the number of cells undergoing apoptosis while proliferation remains unchanged
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• at E13.5, homozygotes invariably display a double outlet right ventricle
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• at E13.5, homozygotes display dysplastic mitral and tricuspid valves; in severe cases, no atrioventricular valves are formed
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• at E13.5, all homozygotes display ventricular septal defects
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• at E13.5, some homozygotes with excessive accumulation of endocardial cushion cells display subsequent right ventricular outflow tract (RVOT) obstruction
• however, no persistent truncus arteriosus is observed
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• at E13.5, homozygotes display a significantly smaller, hypoplastic right ventricle, but a normally-sized left ventricle
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• at >E9.5, many homozygotes exhibit expanded, fluid-filled pericardial sacs
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homeostasis/metabolism
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• at >E9.5, many homozygotes exhibit expanded, fluid-filled pericardial sacs
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muscle
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• at E11.5, all homozygotes exhibit reduced or delayed VSMC formation in the cranial vasculature, dorsal aorta, intersomitic and branchial vessels, although severity is variable
• notably, embryos with the most severe forebrain phenotype show complete absence of VSMCs in the cranial vessels at E11.5
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• at E13.5, the trabecular layer of the mutant myocardium appears thicker and more cellular than normal
• in severe cases, the mutant myocardium appears to be composed almost entirely of the trabecular layer
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• at E13.5, homozygotes exhibit an abnormally thin compact myocardial layer (only 2-3 cells thick) and cells are more closely packed together
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