Analysis Tools
mortality/aging
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• nearly all homozygotes die by embryonic day 13.5, when fetal liver erythropoiesis predominates, and a few survive to E14.5 and E15.5
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liver/biliary system
pale liver
(
J:212530
)
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• homozygous embryos at E15.5 have pale livers deficient in hemoglobinization, with porphyrin accumulation
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hematopoietic system
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• Although the other hematopoietic lineages are normal in homozygotes, at E12.5 erythroid cells are developmentally arrested with a large decrease in the number of TER119 positive cells and normal progenitor R2 population and increased R1 population
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• metabolic labeling shows basal heme synthesis and heme synthesis in differentiating erythroid cells is significantly less than normal, and E15.5 homozygotes are profoundly anemic
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• fetal livers autofluoresce under fluorescence illumination at E12.5 indicative of accumulating heme intermediates
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• protoporphyrin IX synthesis is blocked leading to an accumulation of porphyrin precursors, and there is diminished cellular iron in erythroid cells during differentiation
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