单位：[1]Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA[2]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Neurol,Wuhan 430032,Peoples R China神经内科华中科技大学同济医学院附属同济医院神经科[3]Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 10010, Peoples R China
In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA-box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQrepeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP's interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.
基金：
NIH [AG019206, NS041449, NS095279, NS0405016]; Viral Vector Core of the Emory Neuroscience NINDS Core Facilities grant [P30NS055077]
第一作者单位：[1]Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA[2]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Neurol,Wuhan 430032,Peoples R China
通讯作者：
通讯机构：[1]Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA[*1]Emory Univ, Sch Med, Dept Human Genet, 615 Michael St,Room 355, Atlanta, GA 30322 USA
推荐引用方式(GB/T 7714)：
Huang Shanshan,Yang Su,Guo Jifeng,et al.Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice[J].CELL REPORTS.2015,13(1):196-208.doi:10.1016/j.celrep.2015.08.060.
APA：
Huang, Shanshan,Yang, Su,Guo, Jifeng,Yan, Sen,Gaertig, Marta A....&Li, Xiao-Jiang.(2015).Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice.CELL REPORTS,13,(1)
MLA：
Huang, Shanshan,et al."Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice".CELL REPORTS 13..1(2015):196-208
生物学