Table 1.

RUNX complexes in the immune system

Targeted gene	Phenotype of germline knockout	Refs	Phenotype of conditional knockout	Refs
Runx1	Embryonic lethal between days 12.5 and 13.5 Required for definitive haematopoiesis; no generation of HSCs	16,9	Mx-CRE: Normal HSC numbers Normal myeloid-cell compartment Severe reduction in platelet formation and megakaryocyte differentiation Defective B- and T-cell differentiation	64
			Lck-CRE: De-repression of Cd4 in DN thymocytes Block in T-cell development at DN3 stage	17,24
			Cd4-CRE: Defect in positive selection and maturation of CD4 SP thymocytes Loss of NKT cells	24,45
Runx2	Perinatal lethality Lack of bone formation owing to maturational arrest of osteoblasts	11,65	ND
Runx3	Not lethal; mice are viable Defects in neurogenesis and thymopoiesis Controversial role in the development of gastric epithelial-cell cancer; gastric mucosal hyperplasia and tumour development present12 or absent13 depending on strain of Runx3 knockout mice examined	12,13	Cd4-CRE: De-repression of Cd4 in CD8 SP thymocyte Reduction in CD8 SP thymocyte numbers	24,56
Cbfb	Identical to Runx1 germline knockout (see above)	15, 16,66	Lck-CRE: De-repression of Zbtb7b in CD69− DP thymocytes	42
			Cd4-CRE: De-repression of Zbtb7b in CD4+CD8low peripheral T cells	42
Runx1 and Runx3	Identical to Runx1 germline knockout (see above)		Runx1fl/flRunx3fl/fl* and Cd4-CRE: Loss of CD8 SP thymocytes	24
			Runx1Δ446/Δ446‡, Runx3fl/fl* and Cd4-CRE: Redirection of MHC class I-specific thymocytes to the CD4 lineage De-repression of Zbtb7b	42

^*Runx1 alleles targeted with flanking loxP sites.

^‡Runx1 alleles lack carboxy-terminal VWRPY (Groucho/TLE-binding) motif.

Cbfb, core-binding factor-β; DN, double negative; HSC, haematopoietic stem cell; ND, not determined; NKT, natural killer T; RUNX, runt-related transcription factor; SP, single positive.