Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11

The CBFB-MYH11 gene was introduced into mouse genome by inserting the 3' part of the human MYH11 cDNA into the end of exon 5 of the mouse Cbfb gene through homologous recombination. This led to the creation of a half genomic (Cbfb), half cDNA (MYH11) fusion gene, which, in turn, resulted in the generation of a Cbf(beta)-SMMHC fusion protein under the control of the Cbfb promoter. Cbf(beta)-SMMHC is shown to dominantly suppress the normal function of Cbf gene products and inhibits the differentiation of hematopoietic stem cells.