Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic mice
نویسندگان
چکیده
منابع مشابه
Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic mice.
Huntington's disease (HD) results from the expansion of a glutamine repeat near the N-terminus of huntingtin (htt). At post-mortem, neurons in the central nervous system of patients have been found to accumulate N-terminal fragments of mutant htt in nuclear and cytoplasmic inclusions. This pathology has been reproduced in transgenic mice expressing the first 171 amino acids of htt with 82 gluta...
متن کاملN17 Modifies Mutant Huntingtin Nuclear Pathogenesis and Severity of Disease in HD BAC Transgenic Mice
The nucleus is a critical subcellular compartment for the pathogenesis of polyglutamine disorders, including Huntington's disease (HD). Recent studies suggest the first 17-amino-acid domain (N17) of mutant huntingtin (mHTT) mediates its nuclear exclusion in cultured cells. Here, we test whether N17 could be a molecular determinant of nuclear mHTT pathogenesis in vivo. BAC transgenic mice expres...
متن کاملHaploinsufficiency of Cyfip1 Produces Fragile X-Like Phenotypes in Mice
BACKGROUND Copy number variation (CNV) at the 15q11.2 region, which includes a gene that codes for CYFIP1 (cytoplasmic FMR1 interacting protein 1), has been implicated in autism, intellectual disability and additional neuropsychiatric phenotypes. In the current study we studied the function of Cyfip1 in synaptic physiology and behavior, using mice with a disruption of the Cyfip1 gene. METHODO...
متن کاملHuntingtin and the molecular pathogenesis of Huntingtons disease
Huntington’s disease (HD) is a late-onset neurodegenerative disorder that is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (htt). The normal function of htt, and the molecular mechanisms that contribute to the disease pathogenesis, are in the process of being elucidated. In this review...
متن کاملDiscovery of a novel small-molecule targeting selective clearance of mutant huntingtin fragments.
CAG-triplet repeat extension, translated into polyglutamines within the coding frame of otherwise unrelated gene products, causes 9 incurable neurodegenerative disorders, including Huntington's disease. Although an expansion in the CAG repeat length is the autosomal dominant mutation that causes the fully penetrant neurological phenotypes, the repeat length is inversely correlated with the age ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Human Molecular Genetics
سال: 2004
ISSN: 1460-2083,0964-6906
DOI: 10.1093/hmg/ddh175