mortality/aging
• only ~7% of mutant mice are born, indicating embryonic lethality probably due to vascular and heart anomalies resulting from ectopic cre expression
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embryo
• by day 10 of pregnancy, formation of fetal blood vessels from the allantois is clearly absent
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• at day 9 of pregnancy, but nor earlier, secondary TGC differentiation appears to increase because more cells are present
• by day 10 of pregnancy, many layers of secondary TGC are noted in mutant females relative to control animals
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• at day 9 of pregnancy, the mutant uterus displays a reduced number of decidual sites with the absence of embryo or the presence of growth-retarded embryos
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• by day 10 of pregnancy, mutant placentas show a reduction in spongiotrophoblast cell number relative to wild-type placentas
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• by day 10 of pregnancy, the mutant labyrinth fails to develop
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• at day 9 of pregnancy, but nor earlier, abnormal placenta development and frequent hemorrhages are observed
• by day 10 of pregnancy, the mutant labyrinth fails to develop
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reproductive system
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• mutant females display vaginal bleeding 10-12 days after the presence of a copulatory plug
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• at day 9 of pregnancy, the mutant uterus displays a reduced number of decidual sites with the absence of embryo or the presence of growth-retarded embryos
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• the circular smooth muscle layer of mutant uteri appears disorganized relative to that of wild-type uteri, as shown by anti-smooth muscle actin immunostaining
• in contrast, the mutant endometrium appears relatively normal
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• mutant uterine horns appear shorter than those of control mice
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• upon mating with wild-type males, mutant females exhibit a significant lower number of implantation sites per pregnant female than control females (5.3 2.4 vs 8.8 2.2, respectively)
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• upon mating with wild-type males, mutant females display vaginal bleeding 10-12 days after the presence of a copulatory plug, indicating failure to maintain pregnancy
• at day 9 of pregnancy, most embryos are reabsorbed and a few are growth-retarded
• however, production of endogenous estradiol and progesterone remains unaffected in mutant females
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• despite normal ovarian histology and function, mutant female mice receiving a wild-type ovary are unable to produce pups as observed before ovary transfer
• only 1 of 6 mutant females with wild-type ovaries gave birth to one pup in a 6-month period whereas wild-type females carrying mutant ovaries exhibited normal litter sizes with pups derived from the donor ovary
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cardiovascular system
• by day 10 of pregnancy, formation of fetal blood vessels from the allantois is clearly absent
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hemorrhage
(
J:120852
)
• mutant embryos with hemorrhage are observed
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• mutant females display vaginal bleeding 10-12 days after the presence of a copulatory plug
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homeostasis/metabolism