mortality/aging
• all homozygotes die between E15.5-E17.5 as a result of fatal fetal anemia
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hematopoietic system
• excessive macrophage formation
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• at E15.5, fetal thymus cellularity is reduced to 10% of wild-type controls
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• homozygotes show a complete failure of T and B cell differentiation
• any remaining cells in fetal thymi are B220+CD19- cells, suggesting that lymphocyte differentiation abortively forms B cell precursors instead of T lineage cells
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• at E15.5, homozygotes lack committed B220+CD19+ pro-B cells in fetal liver, unlike wild-type controls
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• at E15.5, B cell differentiation fails to progress beyond the B220+CD19- stage in fetal liver, unlike in wild-type controls
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• at E15.5, homozygotes show a marked expansion of myeloid cells in fetal liver due to a 330% increase in granulocyte/macrophage progenitor numbers in the earliest stages of myeloid lineage
• a significant increase is seen in more mature and granular Mac-1hi (390%) and Gr-1lo (210%) cells
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• terminal granulocyte differentiation in fetal liver is impaired resulting in absence of Gr-1hi cells
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• at E14.5-E15.5, live homozygous fetuses are extremely anemic with a severe deficit of RBCs in vitelline and umbilical circulation
• however, no defect in the production of adult globins nor any chain imbalance in globin is observed, suggesting that thalassemia is not the cause of fetal fatal anemia
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• at E14.5-E15.5, BFU-E and CFU-E counts in fetal liver are reduced by 40% relative to those in heterozygous or wild-type controls
• the numbers of cells in the early to late erythroblast stages of differentiation are reduced 80% relative to those in wild-type controls
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• homozygotes display failure of erythroblast growth and differentiation
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• at E14.5-E15.5, total RBC counts are less than 20% of those in heterozygous or wild-type controls
• mature anucleate erythrocytes are reduced to 10% of controls
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• at E15.5, fetal liver-derived anucleate erythrocytes are scarce; those present are often small and sometimes nucleated
• at E15.5, normoblast numbers are significantly reduced in fetal liver
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• at E14.5-E15.5, live homozygous fetuses display a 4-fold reduction of hematocrit in peripheral blood relative to wild-type controls
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• at E14.5-E15.5, live homozygous fetuses show a 4-fold reduction of hemoglobin levels in peripheral blood relative to wild-type controls
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• at E15.5, Gr-1hi granulocytes are absent in fetal liver
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• at E15.5, homozygotes show complete absence of Thy1+ cells in fetal liver
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• at E15.5, homozygotes show a 390% increase in Mac-1hi cells in fetal liver
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• at E15.5, non-nucleated reticulocyte numbers are significantly reduced in fetal liver
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immune system
• excessive macrophage formation
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• at E15.5, fetal thymus cellularity is reduced to 10% of wild-type controls
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• homozygotes show a complete failure of T and B cell differentiation
• any remaining cells in fetal thymi are B220+CD19- cells, suggesting that lymphocyte differentiation abortively forms B cell precursors instead of T lineage cells
|
• at E15.5, homozygotes lack committed B220+CD19+ pro-B cells in fetal liver, unlike wild-type controls
|
• at E15.5, B cell differentiation fails to progress beyond the B220+CD19- stage in fetal liver, unlike in wild-type controls
|
• at E15.5, homozygotes show a marked expansion of myeloid cells in fetal liver due to a 330% increase in granulocyte/macrophage progenitor numbers in the earliest stages of myeloid lineage
• a significant increase is seen in more mature and granular Mac-1hi (390%) and Gr-1lo (210%) cells
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• terminal granulocyte differentiation in fetal liver is impaired resulting in absence of Gr-1hi cells
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• at E15.5, Gr-1hi granulocytes are absent in fetal liver
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• at E15.5, homozygotes show complete absence of Thy1+ cells in fetal liver
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• at E15.5, homozygotes show a 390% increase in Mac-1hi cells in fetal liver
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liver/biliary system
• at E15.5, fetal liver cellularity is reduced to half that of wild-type controls
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integument
cellular
• terminal granulocyte differentiation in fetal liver is impaired resulting in absence of Gr-1hi cells
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• excessive macrophage formation
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endocrine/exocrine glands
• at E15.5, fetal thymus cellularity is reduced to 10% of wild-type controls
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