期刊
BRAIN RESEARCH
卷 1472, 期 -, 页码 124-137出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2012.06.052
关键词
Fragile X premutation; CGG KI mouse; Trinucleotide repeat disorder; Intranuclear inclusions
资金
- National Institute of Health (NIH) [NINDS RL1 NS062411]
- NIDCR [UL1 DE019583]
- NCRR [UL1 RR024146]
- NSF Center for Biophotonics Science and Technology Internship
The fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder caused by CGG trinucleotide repeat expansions in the fragile X mental retardation 1 (FMR1) gene. The neuropathological hallmark of FXTAS is the presence of ubiquitin-positive intranuclear inclusions in neurons and in astroglia. Intranuclear inclusions have also been reported in the neurons of male CGG KI mice carrying an expanded CGG trinucleotide repeat and used to model FXTAS, but no study has been carried out quantifying inclusions in female CGG KI mice heterozygous for the fragile X premutation. We used histologic and immunocytochemical methods to determine the pathological features of intranuclear inclusions in astroglia and neurons. In female CGG KI mice, ubiquitin-positive intranuclear inclusions were found in neurons and astroglia throughout the brain in cortical and subcortical regions. These inclusions increased in number and became larger with advanced age and increasing CGG repeat length, supporting hypotheses that these pathologic features are progressive across the lifespan. The number of inclusions in neurons was reduced by similar to 25% in female CGG KI mice compared to male CGG KI mice, but not so low as the 50% predicted. These data emphasize the need to evaluate the neurocognitive and pathological features in female carriers of the fragile X premutation with and without FXTAS symptomatology is warranted, as this population shows similar neuropathological features present in male FXTAS patients. (C) 2012 Elsevier B.V. All rights reserved.
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