A valine to glycine substitute at amino acid 205 (V205G) of exon 4 and a floxed neo cassette insertion in the downstream intron were introduced to the gene via homologous recombination. The V205G mutation disrupts the FOG-binding region without affecting DNA-binding ability, and, in humans, results in severe congenital dyserythropoietic anemia and thrombocytopenia. The neo cassette was removed by transient expression of cre recombinase in correctly targeted ES cells. (J:77724)