The C-terminus of CBFß-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis.. Mus musculus

The C-terminus of CBFß-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-mulimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBFß-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBFß-SMMHC (CBFß-SMMHCΔC95). Embryos with a single copy of CBFß-SMMHCDC95 were viable and showed no defects in hematopoiesis, while embryos homozygous for the CBFß-SMMHCΔC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBFß-SMMHCΔC95. To identify gene expression changes induced by CBFß-SMMHCDC95, we compared the gene expression profile in the blood cells of Cbfb+/+, Cbfb+/ΔC95, and CbfbΔC95/ΔC95 embryonic day 12.5 (E12.5) mice. Overall design: Cbfb+/ΔC95 were mated together to generate Cbfb+/+, Cbfb+/ΔC95, and CbfbΔC95/ΔC95 embryos. Blood from 8-10 E12.5 embryos of the same genotype was pooled, and RNA was isolated, labeled, and hybridized to Affymetrix Genechip mouse microarray (430 2.0) chips. 3 chips were used for each genotype.