Analysis of a tissue specific master regulator, PEBP2

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There are three mammalian runt-related genes, Runxl/Amll,Runx2/Cbfal and Runx3/Pebp2αC. The function of Runx3 is poorly understood. To elucidate the function of Runx3, we generated mice that lack of the gene by homologuos recombination.1. In wild type mice, gastric epithelial cells express high levels of Runx3. When Runx3 was knocked out, the gastric mucosa exhibited hyperplasia and normal epithelial apoptosis was suppressed. This may be due to the reduced sensitivity of Runx3-/- epithelial cells to the growth-inhibiting and apoptosis-inducing activities of TGF- β.2. It was reported that Runx3 may be important in immunoglobulin (Ig) class switching from IgM to IgA because of its ability to activate the germline Ig C α promoter. It was seemed that Ig class switching might not be observed in Runx3-/- mice, however, in fact Ig class switching was observed in Runx3-/- mice as in WT mice. The possible involvement of the other Runx family genes in class switching is discussed.3. In the T-cell development, CD4+ or CD8+ single positive T cells develop from CD4+CD8+ double positive T cells. In a Runx3-deficient thymus, CD4+ single positive T cells develop normally but CD8+ single positive T cells do not. It is known that CD4 gene silencing play a role to establish CD8+ single positive T cells. These data demonstrated that Runx3 plays an essential role in CD4 gene silencing.4. Runx3-/- mice with the ICR background weredisplayed marked ataxia. trkC-expressing dorsal root ganglion neurons project their axons to specific target layers in the gray matter of the spinal cord, forming stretch-reflex circuit, however, it was found that proprioceptive afferent axons fail to reach the ventral horn in Runx3 is seemed to be essential for the axon pathfinding of trkC-expressing dorsal root ganglion neurons