Article
Truncation of mutant huntingtin in knock-in mice demonstrates exon1 huntingtin is a key pathogenic form.
Nature communications - 22 May 2020
Yang Huiming, Yang Su, Jing Liang, Huang Luoxiu, Chen Luxiao, Zhao Xianxian, Yang Weili, Pan Yongcheng, Yin Peng, Qin Zhaohui S, Tang Beisha, Li Shihua, Li Xiao-Jiang
Abstract excerpt
Polyglutamine expansion in proteins can cause selective neurodegeneration, although the mechanisms are not fully understood. In Huntington's disease (HD), proteolytic processing generates toxic N-terminal huntingtin (HTT) fragments that preferentially kill striatal neurons. Here, using CRISPR/Cas9 to truncate full-length mutant HTT in HD140Q knock-in (KI) mice, we show that exon 1 HTT is stably present in the...
Topics
- Adaptor Proteins, Signal Transducing
- Age Factors
- Animals
- CRISPR-Cas Systems
- Cell Nucleus
- Corpus Striatum
- Exons
- Female
- Gene Knock-In Techniques
- Huntingtin Protein