波浪/Pax-1突变的分子基础
G Chalepakis1, R Fritsch, H Fickenscher
1Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Göttingen, Federal Republic of Germany.
Cell
|September 6, 1991
概括
配对盒基因Pax-1 (配对盒基因1) 通常会结合DNA并激活转录. 波形小鼠中的突变破坏了Pax-1DNA结合,解释了脊柱形.
科学领域:
- 发育生物学是发展生物学.
- 分子遗传学 分子遗传学
- 结构生物学是结构生物学.
背景情况:
- 鼠配对盒基因Pax-1与波纹 (非) 鼠标突变相关.
- 波浪式突变导致脊柱形,这是由于Pax-1中的特定点突变造成的.
研究的目的:
- 为了研究Pax-1基因的分子功能.
- 确定波纹突变对Pax-1DNA结合特性和转录活性的影响.
主要方法:
- 凝转移测试用于分析DNA结合特异性.
- 结合干扰实验有助于定义DNA结合核心动图.
- 野生类型和突变Pax-1蛋白质的比较分析.
主要成果:
- Pax-1编码了一种具有转录激活特性的DNA结合蛋白.
- 在Pax-1的配对域中的位置15的Gly-Ser交换突变显著降低了DNA结合亲和力.
- 这种突变还改变了Pax-1蛋白的DNA结合特异性.
结论:
- 配对域中的Gly-Ser替代是波浪突变的分子基础.
- 改变的DNA结合和Pax-1的特异性解释了在小鼠中观察到的脊椎形.
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