异位表达的CAG重复会在小鼠中引起核内和逐渐晚发的神经现象
J M Ordway1, S Tallaksen-Greene, C A Gutekunst
1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 35294, USA.
Cell
|December 31, 1997
概括
扩大的CAG重复会导致神经退行性疾病. 在小鼠的Hprt基因中引入CAG重复,为这些疾病创造了一个模型,表明重复背景对神经毒性并不重要.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 几种人类神经退行性疾病与扩展的CAG重复序列有关.
- 在这些扩散的致病性中重复环境的作用仍然不完全理解.
研究的目的:
- 为了研究CAG重复扩张的神经毒性潜力,独立于它们的原生遗传环境.
- 开发一个小鼠模型来研究翻译的CAG重复障碍.
主要方法:
- 将146个单元的CAG重复引入小鼠的低氨酸基转移酶 (Hprt) 基因.
- 产生和表征Hprt突变小鼠表达一个多重胺通道.
- 评估神经现象型,包括发病,进展和生存.
- 对神经元内核内含物进行组织病理学检查.
主要成果:
- 突变小鼠开发了一个渐进的,晚发的神经现象型.
- 受影响的小鼠表现出过早死亡和神经元内核入.
- 在Hprt基因中引入的CAG重复足以引起神经毒性作用.
结论:
- 在已知的疾病相关基因内不存在时,CAG重复扩张可能会产生神经毒性作用.
- 这种Hprt-CAG重复小鼠模型有效地概括了人类翻译的CAG重复障碍的关键特征.
- 重复的背景不是CAG重复诱导的神经退行症的先决条件.
相关概念视频
01:39Mutations
Overview
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...