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Author (up) Wenzel, H.J.; Hunsaker, M.R.; Greco, C.M.; Willemsen, R.; Berman, R.F. url  doi
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  Title Ubiquitin-positive intranuclear inclusions in neuronal and glial cells in a mouse model of the fragile X premutation Type Journal Article
  Year 2010 Publication Brain Research Abbreviated Journal Brain Res  
  Volume 1318 Issue Pages 155-166  
  Keywords Age Factors; Aged; Animals; Brain/metabolism/*pathology; Cell Nucleus/metabolism/*pathology; Cytoplasm/metabolism/pathology; Disease Models, Animal; Female; Fragile X Mental Retardation Protein/genetics; Fragile X Syndrome/metabolism/*pathology; Gene Knock-In Techniques; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroglia/metabolism/*pathology; Neurons/metabolism/*pathology; Sex Factors; Trinucleotide Repeat Expansion; Ubiquitin/*metabolism  
  Abstract 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 the disease is the presence of ubiquitin-positive intranuclear inclusions in neurons and in astrocytes. Ubiquitin-positive intranuclear inclusions have also been found in the neurons of transgenic mice model carrying an expanded CGG((98)) trinucleotide repeat of human origin but have not previously been described in glial cells. Therefore, we used immunocytochemical methods to determine the pathological features of nuclear and/or cytoplasmic inclusions in astrocytes, Bergmann glia, and neurons, as well as relationships between inclusion patterns, age, and repeat length in CGG knock-in (KI) mice in comparison with wild-type mice. In CGG KI mice, ubiquitin-positive intranuclear inclusions were found in neurons (e.g., pyramidal cells, GABAergic neurons) throughout the brain in cortical and subcortical brain regions; these inclusions increased in number and size with advanced age. Ubiquitin-positive intranuclear inclusions were also present in protoplasmic astrocytes, including Bergmann glia in the cerebellum. The morphology of intranuclear inclusions in CGG KI mice was compared to that of typical inclusions in human neurons and astrocytes in postmortem FXTAS brain tissue. This new finding of previously unreported pathology in astrocytes of CGG KI mice now provides an important mouse model to study astrocyte pathology in human FXTAS.  
  Address Department of Neurological Surgery, University of California, Davis; Davis, CA 95618, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0006-8993 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:20051238; PMCID:PMC3086812 Approved no  
  Call Number refbase @ user @ Serial 17013  
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