Analysis Tools
mortality/aging
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• no live homozygous mutant animals were recovered, although they were present at a frequency roughly consistent with Mendelian inheritance throughout embryonic development
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hematopoietic system
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• many large abnormal foci containing macrophage with fragmented DNA
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small thymus
(
J:81474
)
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• cellularity 29% of controls
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• homozygous null mice displayed impaired definitive erythropoiesis in the fetal liver and spleen
• the numbers of CFU-E (colony-forming unit, erythroid) as well as BFU-E (burst-forming unit, erythroid), CFU-G (granulocyte), and CFU-M (macrophage) in the E12.5 fetal liver were similar between wild-type and homozygous null embryos
• diaminofluorene staining revealed that mutant erythroid cells were able to differentiate into hemoglobin-producing cells
• in colonies of CFU-E generated with either wild-type or homozygous null fetal liver cells, about 10% of cells were enucleated
• when homozygous null fetal liver cells were transferred into lethally-irradiated wild-type mice, mature red blood cells were generated from the mutant cells, suggesting that impairment of definitive erythropoiesis was due to a non-cell-autonomous effect
• histochemical analysis of E12.5 to E17.5 mutant fetal livers revealed reduced cellularity relative to wild-type, as well as the presence of abnormal foci of various sizes
• electron transmission microscopy combined with immunohistochemical analysis of E12.5 to E17.5 mutant fetal livers revealed accumulation of a large amount of DNA, as well as the presence of macrophage-like cells which were often surrounded by erythroid cells at various stages of differentiation
• these findings suggested that macrophage enzyme activity is required for degradation of nuclear DNA expelled during erythrocyte maturation
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• some homozygous null embryos became paler than normal at E14.5, and all mutant embryos were severely anemic by E17.5; no other abnormalities besides anemia were observed at E17.5
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• up to E12.5, a normal level of vasculature was noted in the homozygous null embryos and yolk sac
• at E12.5, similar numbers of nucleated primitive erythrocytes were observed in the peripheral blood of wild-type and homozygous null embryos
• however, the number of mature erythrocytes in the peripheral blood of homozygous null embryos was less than 1/10th of that present in normal controls at E17.5
• no hemolysis was observed
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• the peripheral blood of mutant embryos contained nucleated erythrocytes, which were not erythrosin-positive primitive erythrocytes, but appeared to be erythroblasts that had not undergone enucleation
(J:69831)
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immune system
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• many large abnormal foci containing macrophage with fragmented DNA
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small thymus
(
J:81474
)
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• cellularity 29% of controls
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endocrine/exocrine glands
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• many large abnormal foci containing macrophage with fragmented DNA
|
small thymus
(
J:81474
)
|
• cellularity 29% of controls
|
