Analysis Tools
cellular
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• at E17.5, mutant embryos display focal necrosis in the liver
• newborn homozygotes exhibit advanced hepatic tissue necrosis with depletion of red blood cells and increased levels of fibrin(ogen) deposition
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mortality/aging
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• homozygotes delivered by Cesarean section are macroscopically normal but die within 24 hrs of birth
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• most homozygotes (8 of 12) are stillborn in the absence of macroscopic abnormalities
• the rest are severely bruised in the head and die within a few hours of birth
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homeostasis/metabolism
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• homozygotes display severe perinatal consumptive coagulopathy in the brain and liver
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• at E17.5, mutant embryos show normal organ and blood vessel development, but exhibit scattered microvascular thrombosis in the telencephalic region of the brain; early signs of thrombosis are first evident at E12.5 and progress thereafter
• at E17.5 or later, hemostatic brain abnormalities are variable and range from minimal clotting and no bleeding to widespread fibrin deposition in the brain with severe bleeding events in the forebrain near the lateral ventricles
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• late stage embryos (>E17.5) and newborn homozygotes display occasional clotting in the heart
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• late stage embryos (>E17.5) and newborn homozygotes display occasional clotting in the lungs
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liver/biliary system
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• at E17.5, mutant embryos display focal necrosis in the liver
• newborn homozygotes exhibit advanced hepatic tissue necrosis with depletion of red blood cells and increased levels of fibrin(ogen) deposition
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• in severe cases, infiltrating leukocytes are observed in the liver interstitia
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• in severe cases, loss of hepatocytes and deterioration of the extracellular matrix are observed
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• at E17.5, most mutant embryos display increased interstitial fibrin in all liver lobes
• fibrin deposition in the liver is first evident but minimal at E12.5 and progresses thereafter
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cardiovascular system
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• 4 of 12 homozygotes born naturally exhibit severe bruising in the head region (subdural space and brain)
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• newborn homozygotes exhibit extensive brain necrosis with secondary edema and severe bleeding near the brain lateral ventricles, close to sites of fibrin deposition; as a result, intracranial pressures are increased
• dural vessels are significantly dilated but show no signs of bleeding
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behavior/neurological
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• homozygotes delivered by Cesarean section are cared for by the foster mother but fail to nurse
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immune system
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• in severe cases, infiltrating leukocytes are observed in the liver interstitia
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• at E17.5, most mutant embryos display increased interstitial fibrin(ogen) deposition in the liver, which becomes pronounced at birth; fibrin deposition in the liver is first evident but minimal at E12.5
• newborn homozygotes exhibit notable fibrin(ogen) deposition in the brain microvasculature; a small degree of fibrin deposition is first noted in the telencephalon at E12.5-E14.5 near sites of thrombosis
• traces of fibrin deposition are also observed in the glomeruli and tubuli of neonatal kidneys
• homozygotes show absence of plasma clottable fibrinogen both at E17.5 and neonatally, indicating fibrinogen depletion due to consumptive coagulopathy
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nervous system
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• newborn homozygotes exhibit extensive brain necrosis with secondary edema and severe bleeding near the brain lateral ventricles, close to sites of fibrin deposition; as a result, intracranial pressures are increased
• dural vessels are significantly dilated but show no signs of bleeding
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