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Chunk #43 — Results/Discussion — Discussion

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Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells.
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In this work we report a post-implantation lethal phenotype for mutations in Bptf, the previously characterized largest subunit of the NURF chromatin remodeling complex [15]. In the early embryo Bptf is expressed by E4.5 in the ICM and primitive endoderm. At later stages of development Bptf is expressed in both embryonic and extra-embryonic ectoderm by E5.5. Following gastrulation, Bptf is widely expressed in all germ layers to E13.5. Bptf expression is essential for early development because homozygous Bptf mutant embryos are reabsorbed by E8.5. No overt defects were observed in the mutant E3.5 or E4.5 embryo or its ability to proliferate in culture, suggesting that Bptf embryos undergo a normal initial specification and proliferation of the ICM, primitive endoderm and trophectoderm. However, mutant embryos exhibit diminished proliferation post-implantation as shown by defects in size of both extra-embryonic and embryonic tissues and decreased phosphorylated histone H3 staining. A histological analysis of mutant embryos at E6.5 and E7.5 revealed that they develop a VE but do not form a primitive streak or differentiate mesoderm. To investigate the causes of the defect in