Analysis Tools
mortality/aging
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• on a mixed genetic background, homozygotes display a progressive decline in survival between E11.5 and E16.5; no homozygotes are recovered past E16.5
• Background Sensitivity: on an inbred 129 background, homozygotes die between E11.5 and E13.5
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embryo
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• starting at E11.5, homozygous mutant embryos appear developmentally retarded relative to wild-type or heterozygous controls
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• at E12.5, homozygous mutant embryos are smaller than normal
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• homozygous mutant embryos display a ~20% weight reduction by E12.5 relative to controls embryos
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• at E12.5, the mutant spongiotrophoblast layer is reduced in size relative to that in wild-type controls
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• at E12.5, the mutant labyrinth layer is reduced in size and contains numerous mesenchymal cells relative to that in wild-type controls
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• at E12.5, the mutant labyrinth layer is poorly vascularized
• in contrast, the decidua appears normal
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• at E12.5, mutant placentas are smaller than normal
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• mutant placentas show a ~20% weight reduction by E12.5 relative to control placentas
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growth/size/body
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• starting at E11.5, homozygous mutant embryos appear developmentally retarded relative to wild-type or heterozygous controls
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• at E12.5, homozygous mutant embryos are smaller than normal
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• homozygous mutant embryos display a ~20% weight reduction by E12.5 relative to controls embryos
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liver/biliary system
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• at E12.5, mutant liver sinuses contain fewer red blood cells than wild-type
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• at E12.5, most mutant hepatoblasts (but not erythroid cells) exhibit numerous pyknotic and fragmented nuclei, as shown by immunohistochemical staining
• at E12.5, TUNEL analysis of mutant livers revealed an increased level of apoptosis mainly in the hepatoblast compartment
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• at E12.5, mutant liver cells appear slightly enlarged relative to wild-type cells
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small liver
(
J:69056
)
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• at E12.5, mutant livers are significantly smaller than wild-type
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• at E12.5, mutant livers are hypocellular relative to control livers
• however, no defect in hepatoblast proliferation is observed, as determined by PCNA staining
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pale liver
(
J:69056
)
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• at E12.5, mutant livers are very pale
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cardiovascular system
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• at E12.5, mutant liver sinuses contain fewer red blood cells than wild-type
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• at E12.5, the mutant labyrinth layer is poorly vascularized
• in contrast, the decidua appears normal
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cellular
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• mutant MEFs immortalized according to the 3T3 protocol lose their hypersensitivity towards actinomycin D-induced apoptosis
• 3T3-like mutant cells are resistant to the cytotoxic effects of TNF alone, but are as susceptible as wild type cells to a combination of TNF plus cycloheximide
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• primary MEFs established from E11.5-E12.5 mutant embryos are more susceptible than wild type to apoptosis induced by growth factor deprivation and actinomycin D treatment
• mutant MEFs immortalized according to the 3T3 protocol are more susceptible than wild-type cells to Fas activation
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• in asynchronous cultures, multipotent hematopoietic precursors established from E11.5 mutant livers display a >5-fold increase in spontaneous apoptosis relative to wild-type hematopoietic cells, as shown by annexin V staining
• no significant defects in proliferation of mutant fetal liver cells are observed in vitro
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• in culture, primary MEFs established from E11.5-E12.5 mutant embryos exhibit a >4-fold increase in apoptosis relative to wild-type MEFs, as shown by TUNEL staining; in contrast, the number of S-phase MEFs is similar, arguing against a cell cycle defect `
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• at E12.5, most mutant hepatoblasts (but not erythroid cells) exhibit numerous pyknotic and fragmented nuclei, as shown by immunohistochemical staining
• at E12.5, TUNEL analysis of mutant livers revealed an increased level of apoptosis mainly in the hepatoblast compartment
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integument
