Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor β

K. Sasaki, H. Yagi, R. T. Bronson, K. Tominaga, T. Matsunashi, K. Deguchi, Y. Tani, T. Kishimoto, T. Komori

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330 Scopus citations

Abstract

Core binding factor β (CBFβ) is considered to be a transcriptional coactivator that dimerizes with transcription factors core binding factor α 1 (CBFA1), -2, and -3, and enhances DNA binding capacity of these transcription factors. CBFβ 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 CBFβ, 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.

Original languageEnglish
Pages (from-to)12359-12363
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number22
DOIs
StatePublished - 1996
Externally publishedYes

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