Progressive Spatial Processing Deficits in a Mouse Model of the Fragile X Premutation

Michael R. Hunsaker, H. Jürgen Wenzel, Rob Willemsen, Robert F Berman

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that is the result of a CGG trinucleotide repeat expansion in the range of 55-200 in the 5′ UTR of the FMR1 gene. To better understand the progression of this disorder, a knock-in (CGG KI) mouse was developed by substituting the mouse CGG8 trinucleotide repeat with an expanded CGG98 repeat from human origin. It has been shown that this mouse shows deficits on the water maze at 52 weeks of age. In the present study, this CGG KI mouse model of FXTAS was tested on behavioral tasks that emphasize spatial information processing. The results demonstrate that at 12 and 24 weeks of age, CGG KI mice were unable to detect a change in the distance between two objects (metric task), but showed intact detection of a transposition of the objects (topological task). At 48 weeks of age, CGG KI mice were unable to detect either change in object location. These data indicate that hippocampal-dependent impairments in spatial processing may occur prior to parietal cortex-dependent impairments in FXTAS.

Original languageEnglish (US)
Pages (from-to)1315-1324
Number of pages10
JournalBehavioral Neuroscience
Volume123
Issue number6
DOIs
StatePublished - Dec 2009

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Keywords

  • fragile X premutation
  • metric
  • spatial pattern separation
  • spatial processing
  • topological

ASJC Scopus subject areas

  • Behavioral Neuroscience

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