Cbfb Knockout mouse models

Cbfb, ortholog of human CBFB, encodes core binding factor beta, a non-DNA-binding subunit that heterodimerizes with the Runt domain of RUNX1, RUNX2, or RUNX3, allosterically increasing DNA affinity and protecting those factors from ubiquitin-mediated turnover. Loss of the heterodimer collapses definitive hematopoietic emergence from hemogenic endothelium, and homozygous deletion is embryonic lethal near E12.5 with central nervous system hemorrhage, so viable analysis requires conditional alleles or knockin rescue strategies. In leukemia the dominant lesion is the inversion 16 CBFB-MYH11 fusion, whose smooth muscle myosin tail sequesters RUNX1 into transcriptionally inert complexes, a dominant-negative mechanism no simple null reproduces. Model design therefore forks cleanly between conditional deletion for dosage and lineage specification questions and a Cre-inducible fusion knockin for core binding factor leukemia. Because all three RUNX paralogs share this beta subunit, Cbfb loss removes their activities simultaneously, so interpret compound phenotypes with that breadth in mind.

Whole body loss of Cbfb gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.