mortality/aging
• homozygotes usually die at E15, presumably of anoxia
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hematopoietic system
• only rare, immature monocytoid cells are identifiable in mutant liver touch preparations at E15
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• at E15, peripheral blood smears of homozygous mutant fetuses display predominantly large, nucleated yolk-sac derived erythrocytes, with only a few (~20%) non-nucleated erythrocytes typical of liver-derived erythropoiesis, indicating a defect in adult-type erythropoiesis
• in contrast, embryonic erytrhopoiesis appears largely unaffected
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• only rare, diffusely distributed erythroid cells are identifiable in mutant liver touch preparations at E15
• however, no significant differences in megalokaryocyte number or morphology are observed relative to control littermates
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• whereas hematocrits of wild-type and heterozygous fetuses remain in the 30%-40% range between E12 and E15, those of homozygous mutant fetuses drop significantly to values of ~5% between E13 and E15
• by E15, homozygous mutant fetuses show a 10-fold reduction in hematocrit levels relative to wild-type or heterozygous controls
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• at E13-E15, homozygous mutant embryos exhibit a high % of nucleated RBCs (~80%) relative to wild-type and heterozygous embryos (<5%), indicating persistence of yolk-sac derived primitive erythrocytes
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• at least 88% less CFU-GM progenitor cells are identifiable in mutant livers at E14 and E15
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liver/biliary system
• no erythropoietic islands are detectable in mutant liver sinusoids at E15
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small liver
(
J:43747
)
• at E14 and E15, mutant livers are grossly smaller than normal
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cardiovascular system
• no erythropoietic islands are detectable in mutant liver sinusoids at E15
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integument
• at E15, homozygous mutant fetuses are grossly normal in size and shape but appear significantly pale
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