Cbfb Conditional 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.

A floxed Cbfb allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.