FBP knock-out leads to a hematopoietic maturation defect

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NCI	MOLBIO-15

Authors

• W Zhou
• Y Chung
• J Liu
• E Parrilla Castellar
• L Tessarollo
• P Aplan
• D Levens

Abstract

The FarUpStream Element (FUSE) Binding Protein (FBP) is a pivotal protein to regulate c-Myc expression. By targeting the DNA binding domain of FBP, we successfully generated FBP knock out mutant embryos and MEFs (Mouse Embryonic Fibroblasts). Western blot and qPCR demonstrated that the protein and mRNA levels of c-Myc are significantly decreased in the FBP knock-out MEF cells. We also detected decreased c-Myc expression in FBP knock out mouse embryonic livers, their major hematopoietic organs. FACS assay showed a significant decrease of Ter-119, a marker for red blood cells, and B220, which is a major cell surface glycoprotein on lymphoid cells, in FBP knock out embryonic liver cells. Further study demonstrated that FBP knock out fetuses have more hematopoietic stem cells (HSC) than the wild-type and fewer granulocyte, monocyte and erythroid colony forming units. We also observed a significant loss of megakaryocytes in the FBP knock out embryonic livers. Putting all these data together, suggests that FBP inhibits HSC differentiation but permits HSC proliferation. The FBP knock out is embryo lethal. FBP knock out embryos die progressively from E12.5 till full-term. FBP knock out fetal placentas have severe calcifications compare to other genotypes, they also suffer pulmonary hypoplasia.

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