Analysis of a tissue specific master regulator, PEBP2

哺乳动物矮子相关基因有Runxl/Amll、Runx2/Cbfal和Runx3/Pebp2αC三个。人们对Runx3的功能知之甚少。为了阐明Runx3的功能，我们通过同源重组产生了缺乏该基因的小鼠。在野生型小鼠中，胃上皮细胞高水平表达Runx3。敲除Runx3后，胃黏膜出现增生，正常上皮细胞凋亡受到抑制。这可能是由于Runx3-/-上皮细胞对TGF- β 2抑制生长和诱导凋亡活性的敏感性降低所致。据报道，Runx3可能在免疫球蛋白（Ig）类从IgM到IgA的转换中起重要作用，因为它能够激活种系Ig C α启动子。在Runx3-/-小鼠中似乎没有观察到Ig类转换，但实际上在Runx3-/-小鼠中与WT小鼠一样观察到Ig类转换。讨论了其他Runx家族基因在班级转换中的可能参与。在T细胞发育过程中，CD4+或CD8+单阳性T细胞由CD4+CD8+双阳性T细胞发育而来。在runx3缺陷胸腺中，CD4+单阳性T细胞正常发育，而CD8+单阳性T细胞不正常发育。已知CD4基因沉默在CD8+单阳性T细胞的建立中起作用。这些数据表明Runx3在CD4基因沉默中起重要作用。具有ICR背景的Runx3-/-小鼠表现出明显的共济失调。表达trkc的背根神经节神经元将其轴突投射到脊髓灰质的特定靶层，形成拉伸反射回路，但在Runx3中发现本体感觉传入轴突未能到达腹角，这似乎是表达trkc的背根神经节神经元轴突寻路所必需的

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