Runx1 Conditional Knockout mouse models

Definitive hematopoiesis requires Runx1, the mouse ortholog of human RUNX1 (AML1), a Runt domain transcription factor that heterodimerizes with CBFB to raise DNA affinity at core enhancer TGTGGT motifs and recruits either coactivators such as CBP or corepressors including NCOR-HDAC and GFI1 machinery, governing endothelial to hematopoietic transition, megakaryocyte maturation, and lymphoid development. Disease alleles are mechanistically diverse: germline heterozygous mutations cause familial platelet disorder with predisposition to myeloid malignancy, somatic point mutations cluster in the Runt domain in myelodysplastic syndrome and acute myeloid leukemia, and translocations generate RUNX1-RUNX1T1 or ETV6-RUNX1 chimeras that convert the factor into a dominant repressor. Because germline nulls die around midgestation lacking definitive hematopoietic stem cells, conditional nulls with Vav1-cre or Mx1-cre are essential, while knockin of Runt domain point mutants or endogenous fusion alleles addresses dominant negative mechanism. Paralogs Runx2 and Runx3 share CBFB and DNA motifs, so lineage compensation should be tested explicitly.

Runx1 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.