Chalepakis G, Fritsch R, Fickenscher H, Deutsch U, Goulding M, Gruss P
Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Göttingen, Federal Republic of Germany.
Cell. 1991 Sep 6;66(5):873-84. doi: 10.1016/0092-8674(91)90434-z.
The murine paired box gene Pax-1 has been associated with the mouse developmental mutant undulated (un), which exhibits malformations in the vertebral column. In un mice, a point mutation leading to a Gly-Ser exchange in a conserved part of the paired domain of Pax-1 is present. Here we show that Pax-1 encodes a DNA-binding protein with transcriptional activating properties. The DNA-binding specificity of the Pax-1 protein has been extensively analyzed in gel shift assays, and in conjunction with binding interference experiments, a DNA-binding core motif was defined. Comparison of the DNA-binding properties of wild-type and un Pax-1 proteins demonstrates that the Gly-Ser replacement at position 15 within the paired domain dramatically decreases the DNA-binding affinity of the un Pax-1 protein and alters its DNA-binding specificity. These results decipher the molecular basis of the un mutation.
小鼠配对盒基因Pax-1与小鼠发育突变体“起伏”（un）相关，该突变体在脊柱中表现出畸形。在un小鼠中，存在一个点突变，导致Pax-1配对结构域保守部分的甘氨酸-丝氨酸交换。在这里，我们表明Pax-1编码一种具有转录激活特性的DNA结合蛋白。通过凝胶迁移实验对Pax-1蛋白的DNA结合特异性进行了广泛分析，并结合结合干扰实验，确定了一个DNA结合核心基序。野生型和un Pax-1蛋白的DNA结合特性比较表明，配对结构域内第15位的甘氨酸-丝氨酸替换显著降低了un Pax-1蛋白的DNA结合亲和力，并改变了其DNA结合特异性。这些结果揭示了un突变体的分子基础。
