HEMATOPOIESIS IN THE FETAL LIVER IS IMPAIRED BY TARGETED MUTAGENESIS OF A GENE ENCODING A NON-DNA BINDING SUBUNIT OF THE TRANSCRIPTION FACTOR, POLYOMAVIRUS ENHANCER-BINDING PROTEIN 2 CORE BINDING-FACTOR/

The PebpbZ gene encodes a non-DNA binding subunit of the heterodimeric transcription factor, polyomavirus enhancer binding protein 2/core bi nding factor (PEBP2/CBF), and is rearranged in inversion of chromosome 16 associated with human acute myeloid leukemia, To investigate its p hysiological function, Pebpb2 was mutated by a targeting strategy to g enerate a null mutant, The homozygous mutation in mice proved lethal i n embryos around embryonic day 12.5, apparently due to massive hemorrh aging in the central nervous system. In addition, definitive hematopoi esis in the liver was severely impaired, The observed phenotype was in distinguishable from that reported for homozygous disruption of AML1, which encodes a DNA binding subunit of PEBP2/CBF, Thus, the results in dicate that the two subunits function together as a heterodimeric PEBP 2/CBF in vivo and that PEBP2/CBF plays an essential role in the develo pment of definitive hematopoiesis.