Analysis Tools
mortality/aging
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• only 3 homozygote pups are found among 954 littermates generated from heterozygote intercrosses
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• the three mice that survive the postnatal period die before 18 months of age
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• viable embryos are found at E17.5 and E18.5 though at numbers much lower than expected
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growth/size/body
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• fetal growth slows around E13.5 with significant weight differences occurring by E16.5
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embryo
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• reduced and disordered vascularization of the labyrinth layers of the placenta occurs with defective intermingling of the fetal and maternal vessels
• this defect occurs to homozygote embryos developing in heterozygote mothers
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digestive/alimentary system
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• goblet cells are completely absent throughout the intestinal tract of E17.5 embryos
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• enterocytes of E17.5 embryos are hyperproliferative with proliferation being found in the small intestine villi and throughout the colon epithelium
• small intestine enteroycte proliferation is double that of controls
• large intestine enterocytes are almost all proliferating
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• chromogranin staining reveals few cells in E17.5 intestinal epithelium are differentiating down the enteroendocrine cell pathway
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• enterocytes of E17.5 embryos are hyperproliferative, have enlarged nucei and have lost apical-basal polarity
• enterocytes are found in multiple layers with pseudostratification
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• enterocyte numbers in E17.5 embryos are greatly increased due to the pseudostratification and hyperproliferation
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• dysplasia occurs in E17.5 large intestine with almost all colon enterocytes actively proliferating
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• proliferation of enterocytes occurs throughout the villus in E17.5 embryos instead of being restricted to the crypt bases
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• microvilli are poorly developed and less densely packed in E17.5 embryos
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respiratory system
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• immature differentiation of lung epithelial tissue in noted in E17.5 embryos
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• hyperplasia of the lung epithelium occurs in E17.5 embryos
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endocrine/exocrine glands
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• dysplasia occurs in E17.5 large intestine with almost all colon enterocytes actively proliferating
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homeostasis/metabolism
vision/eye
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• retina epithelial hyperplasia occurs in E17.5 embryos
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neoplasm
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• in the three mice that survive the postnatal period
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integument
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• expression of the late keratinocyte markers loricrin and filaggrin are down regulated in the skin of E17.5 embryos
• there are also increased numbers of keratin-10 expressing cells in the subrabasal layer
• keratinocytes in vivo fail to stop proliferating and terminally differentiate
• cultured keratinocytes fail to stop cell cycling in response to TGF-beta1 or LiCl treatment
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• hair follicles in E17.5 embryos are rarely seen with those present being underdeveloped
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• the basal layer of the epidermis is more dense with cells losing their columnar morphology
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• nucleated cells are present in the cornified layer of the epidermis of E17.5 embryos
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• nucleated cells are present in the granular layer of the epidermis of E17.5 embryos
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• E17.5 embryos have an expanded suprabasal layer of the epidermis that is less differentiated than controls, with reduced enucleation
• cells are proliferating at a higher rate and have less apoptosis than in controls
• suprabasal mutant keratinocytes fail to stop proliferating and terminally differentiate
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• epidermal hyperplasia is evident in E17.5 embryos with epidermal cells have higher rates of proliferation
• epidermal proliferation is 50% higher than in controls
• cell cycle analysis reveals that epidermal cells are defective in cell-cycle exit
• cultured keratinocytes fail to stop cell cycling in response to TGF-beta1 or LiCl treatment
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cardiovascular system
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• reduced and disordered vascularization of the labyrinth layers of the placenta occurs with defective intermingling of the fetal and maternal vessels
• this defect occurs to homozygote embryos developing in heterozygote mothers
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cellular
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• goblet cells are completely absent throughout the intestinal tract of E17.5 embryos
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• expression of the late keratinocyte markers loricrin and filaggrin are down regulated in the skin of E17.5 embryos
• there are also increased numbers of keratin-10 expressing cells in the subrabasal layer
• keratinocytes in vivo fail to stop proliferating and terminally differentiate
• cultured keratinocytes fail to stop cell cycling in response to TGF-beta1 or LiCl treatment
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• enterocytes of E17.5 embryos are hyperproliferative with proliferation being found in the small intestine villi and throughout the colon epithelium
• small intestine enteroycte proliferation is double that of controls
• large intestine enterocytes are almost all proliferating
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liver/biliary system
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• in the three mice that survive the postnatal period
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