PDF(Pubmed)
Abstract：
Somatic instability of the huntingtin (HTT) CAG repeat mutation modifies age-at-onset of Huntington\'s disease (HD). Understanding the mechanism and pathogenic consequences of instability may reveal therapeutic targets. Using small-pool PCR we analyzed CAG instability in the OVT73 sheep model which expresses a full-length human cDNA HTT transgene. Analyses of five- and ten-year old sheep revealed the transgene (CAG)69 repeat was remarkably stable in liver, striatum, and other brain tissues. As OVT73 sheep at ten years old have minimal cell death and behavioral changes, our findings support instability of the HTT expanded-CAG repeat as being required for the progression of HD.
摘要：
亨廷顿（HTT）CAG重复突变的体细胞不稳定性改变了亨廷顿氏病（HD）的发病年龄。了解不稳定性的机制和致病后果可能揭示治疗靶标。使用小池PCR，我们分析了表达全长人cDNAHTT转基因的OVT73绵羊模型中的CAG不稳定性。对五岁和十岁绵羊的分析表明，转基因（CAG）69重复序列在肝脏中非常稳定，纹状体,和其他脑组织。由于10岁的OVT73绵羊的细胞死亡和行为变化很小，我们的发现支持HTT扩展-CAG重复序列的不稳定性是HD进展所必需的.
