mortality/aging
• the remaining neonates died within an hour after birth
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• homozygotes were present at the expected ratios until E15.5
• about 50% of embryos died at E18.5
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integument
• mice exhibit a failure of nerve-vessel alignment in developing limb skin compared with wild-type mice
• however, vascular density is normal
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cardiovascular system
N |
• at E18.5, most major blood vessels, including the superior mesenteric artery (SMA) and vein (SMV), appeared histologically normal
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• mice exhibit a failure of nerve-vessel alignment in developing limb skin compared with wild-type mice
• however, vascular density is normal
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• at E11.5, mutant embryos displayed a normal highly-branched vascular network in the gastrointestinal tract
• at E13.5, mutant mesenteries contained abnormally smaller branches of superior mesenteric artery (SMA) or vein (SMV) relative to wild-type
• at E13.5, wild-type mesenteries contained the SMA, SMV and their paired branches (each branch contained the artery and the vein); in contrast, most of the mutant branches were single
• at E17.5, wild-type large mesenteric vessels were split into many branches and reached one side of the intestine; in mutant embryos large mesenteric vessels were almost absent, and there were fewer large vessels with aberrant branching
• similarly, the large vessels of the stomach arising from the mesenchymal vessels were absent at E15.5; in contrast, the small vascular network that surrounds the stomach remained unaffected
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• disorganized branching patterns in developing limb skin
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• reduced connections between the superior mesenteric artery and the capillary plexus of the midgut loop at E15.5
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• reduced smooth muscle cell coverage of small diameter branched vessels
• however, coverage of large diameter veins is normal
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• sometimes fused as well
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• at E14.5
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• at E18.5, mutant embryos displayed defects of the membranous portion of the cardiac ventricular septum
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• double outlet at E14.5
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• at E16.5, mutant embryos had multiple hemorrhages and/or congestion in the small intestine
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digestive/alimentary system
N |
• the stomachs and intestines of E18.5 mutant embryos were grossly normal
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• at E16.5, mutant embryos had multiple hemorrhages and/or congestion in the small intestine
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embryo
N |
• homozygous null embryos showed normal formation of large and small vessels in the yolk sac (E12.5, E14.5), head region, (E11.5), and developing heart (E12.5-14.5)
• vitellin and umbilical vessels appeared normal
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hematopoietic system
• fetal livers displayed a severe reduction in the number of B-cell progenitors
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• developing hematopoietic cells found in wild-type bone marrow were absent in mutant bone marrow
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immune system
• fetal livers displayed a severe reduction in the number of B-cell progenitors
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• developing hematopoietic cells found in wild-type bone marrow were absent in mutant bone marrow
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muscle
• reduced smooth muscle cell coverage of small diameter branched vessels
• however, coverage of large diameter veins is normal
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nervous system
N |
• mice exhibit normal innervation accompanied by migrating Schwann cells
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