mortality/aging
• homozygotes die between E10.5 and E12.5
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liver/biliary system
• at E9.5, homozygotes display absence of a typical liver bud; a thicker liver-like capsule and matrix-like structures are observed at E11.5, consisting of mesenchymal and undifferentiated endodermal cells
• at E10.5 and E11.5, the size of the liver-like structure is significantly reduced
• surprisingly, no histologic abnormalities are observed in the lung, thyroid or any other endoderm-derived tissue at E11.5; no malformation of neural development is noted
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• at E9.5, homozygotes display absence of a typical liver bud
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• although hematopoietic cells are found within the sinusoidal spaces, no parenchymal hepatocytes or apoptotic cells are histologically detected in the liver-like structure at E10.5 and E11.5
• at E8.5, mutant livers display absence of albumin expression; at E11.5, expression of several transcription factors involved in hepatocyte differentiation is reduced while expression of others is restricted to the capsule and internal matrix-like structures, indicating presence of undifferentiated endodermal cells
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hematopoietic system
• at E10.5, homozygotes show impaired hematopoetic differentiation of the monocyte lineage, with significantly reduced granulocytic-macrophage colony counts in isolated yolk sacs; in contrast, the erythroid lineage remains unaffected
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• at E11.5, homozygotes display impaired definitive hematopoiesis in liver due to arrested hepatogenesis, as shown by reduced beta-major globin mRNA levels
• however, definitive hematopoiesis is unaffected in other sites (aorta-gonad-mesonephros region and peripheral blood), as shown by histological and colony-formation assays
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immune system
• at E10.5, homozygotes show impaired hematopoetic differentiation of the monocyte lineage, with significantly reduced granulocytic-macrophage colony counts in isolated yolk sacs; in contrast, the erythroid lineage remains unaffected
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cellular
• at E10.5, homozygotes show impaired hematopoetic differentiation of the monocyte lineage, with significantly reduced granulocytic-macrophage colony counts in isolated yolk sacs; in contrast, the erythroid lineage remains unaffected
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