Absence of Fetal Liver Hematopoiesis in Mice Deficient in Transcriptional Coactivator Core Binding Factor $\beta

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 22; pp. 12359 - 12363
• Main Authors: Sasaki, Koichi, Yagi, Hideshi, Bronson, Roderick T., Tominaga, Kumi, Matsunashi, Tatsuro, Deguchi, Kenji, Tani, Yoshihiko, Kishimoto, Tadamitsu, Komori, Toshihisa
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 29.10.1996; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Central Nervous System - blood supply; Central Nervous System - embryology; Core Binding Factor beta Subunit; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Embryos; Exons; Fetuses; Genes; Hematopoiesis; Hematopoietic stem cells; Hemorrhage; Hemorrhage - genetics; Heterozygotes; Homozygote; Homozygotes; Humans; Knockout mice; Liver; Liver - embryology; Liver - physiology; Mice; Mice, Knockout; Mutagenesis; Polymerase Chain Reaction; Prenatal development; Rodents; Transcription Factor AP-2; Transcription Factors - genetics; Transcription Factors - physiology; Yolk sac
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.22.12359

Core binding factor $\beta $ (CBF$\beta $) is considered to be a transcriptional coactivator that dimerizes with transcription factors core binding factor $\alpha $ 1 (CBFA1), -2, and -3, and enhances DNA binding capacity of these transcription factors. CBF$\beta $ and CBFA2, which is also called acute myeloid leukemia 1 gene, are frequently involved in chromosomal translocations in human leukemia. To elucidate the function of CBF$\beta $, mice carrying a mutation in the Cbfb locus were generated. Homozygous mutant embryos died between embryonic days 11.5-13.5 due to hemorrhage in the central nervous system. Mutant embryos had primitive erythropoiesis in yolk sac but lacked definitive hematopoiesis in fetal liver. In the yolk sac of mutant embryos, no erythroid or myeloid progenitors of definitive hematopoietic origin were detected, and the expression of flk-2/flt-3, the marker gene for early precursor cells of definitive hematopoiesis, was absent. These data suggest that Cbfb is essential for definitive hematopoiesis in liver, especially for the commitment to early hematopoietic precursor cells.