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Behav Brain Res. 2010 Dec 1;213(2):263-8. doi: 10.1016/j.bbr.2010.05.010. Epub 2010 May 15.

Temporal ordering deficits in female CGG KI mice heterozygous for the fragile X premutation.

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Program in Neuroscience, University of California-Davis, 1515 Newton Court, Davis, CA 95616, USA.


The fragile X premutation is a tandem CGG trinucleotide repeat expansion on the FMR1 gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse with CGG repeat lengths between 70 and 350 has been developed and used to characterize the histopathology and cognitive deficits reported in carriers of the fragile X premutation. Previous studies have shown that CGG KI mice show progressive deficits in processing spatial information. To further characterize cognitive deficits in the fragile X premutation, temporal ordering in CGG knock-in (CGG KI) mice was evaluated. Female CGG KI mice were tested for their ability to remember the temporal order in which two objects were presented. The results demonstrate that at 48 weeks of age, female CGG KI mice with CGG repeat expansions between 150 and 200 CGG repeats performed more poorly on tests of temporal order than wildtype mice, whereas female CGG KI mice with between 80 and 100 CGG repeats performed similarly to wildtype mice. No mice had any difficulty in detecting the presence of a novel object. These data suggest female CGG KI mice show a CGG repeat length-sensitive deficit for temporal ordering.

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