mortality/aging
• a few homozygotes survive until E8.5-E10.5, but are extremely underdeveloped, often severely disorganized, and/or undergoing resorption
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• homozygotes rarely survive beyond E7.5; however, the expected ratios are recovered up until and including this timepoint
• most mutant embryos die between E7.5 and E8.5
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embryo
• at E7.5, 13% of mutant embryos are misoriented with respect to the antimesometrial-mesometrial axis of the deciduum
• in extreme cases, mutant embryos are rotated 180 with respect to their expected positioning within the decidua
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• at E7.5, ~70% of mutant embryos display a defective primary embryonic axis (ultimately the dorsoventral axis), as they are abnormally oriented with respect to the extraembryonic membranes
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• in some cases, mesoderm forms but accumulates as a large mass of loosely associated cells
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• at E7.5, several mutant embryos lack mesoderm formation, indicating failure to undergo gastrulation
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• at E7.5, all mutant embryos exhibit growth retardation and are consistently smaller than wild-type embryos
• mutant embryos surviving to E10.5 exhibit an overall size and developmental stage that is representative of E8.0 wild-type embryos
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• at E7.5, the mutant epiblast is typically smaller and developmentally retarded
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• at E7.5, several mutant embryos show absence of mesoderm formation
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• at E7.5, homozygotes frequently lack organized structures such as a primitive streak
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• at E7.5, 15%-20% of mutant embryos exhibit severe disorganization, such that distinct embryonic and extraembryonic compartments are not identifiable
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• at E7.5, the boundary between embryonic and extraembryonic ectoderm is often poorly defined
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• at E7.5, mutant embryos show disruption of the maternal-embryonic interface, and defective extraembryonic tissue development
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• at E7.5, mutant embryos exhibit a severe reduction in the number of trophoblast giant cells (only 1 or 2 primary giant cells) relative to wild-type embryos (50 to 60)
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• at E7.5, a number of developmentally delayed mutants lack an ectoplacental cone
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• at E7.5, the mutant ectoplacental cone is typically small, compact, and not well-integrated with the surrounding maternal tissues
• in most cases, large pools of maternal blood are found in the decidua adjacent to, but not continuous with, the ectoplacental cone
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• at E7.5, mutant embryos rarely possess an allantoic bud
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• at E7.5, the ectoplacental cavities usually fail to form; in contrast, the proamniotic cavity is present in most mutant embryos
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• at E7.5, the exocoelomic cavities usually fail to form
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• at E7.5, most mutant embryos display a disorganized extraembryonic ectoderm that is either abnormally elongated or resembles a series of folds stacked upon one another
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• at E7.5, mutant embryos with a defective primary embryonic axis show abnormal bending accompanied by malformation of Reichert's membrane
• occasionally, the Reichert's membrane appears to encapsulate the embryo, sometimes as an abnormally thick and continuous layer
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• at E7.5, homozygotes display underdeveloped or disorganized extraembryonic tissues
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growth/size/body
• at E7.5, all mutant embryos exhibit growth retardation and are consistently smaller than wild-type embryos
• mutant embryos surviving to E10.5 exhibit an overall size and developmental stage that is representative of E8.0 wild-type embryos
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