Reduced activity-dependent protein levels in a mouse model of the fragile X premutation

• Published in: Neurobiology of learning and memory 2014-03, Vol.109, p.160-168
• Main Authors: von Leden, Ramona E., Curley, Lindsey C., Greenberg, Gian D., Hunsaker, Michael R., Willemsen, Rob, Berman, Robert F.
• Format: Article
• Language: English
• Subjects: Animal cognition; Animals; Arc; Behavioral psychophysiology; Biological and medical sciences; c-Fos; CGG KI mouse; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Disease Models, Animal; Endophenotype; Fmrp; Fragile X Mental Retardation Protein - genetics; Fragile X Mental Retardation Protein - metabolism; Fragile X premutation; Fragile X Syndrome - genetics; Fragile X Syndrome - metabolism; Fundamental and applied biological sciences. Psychology; Gene Knock-In Techniques; Male; Medical genetics; Medical sciences; Mice; Motor Activity - physiology; Motor Cortex - metabolism; Mutation; Neurobiology; Proteins; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rodents; Western blot
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2014.01.011

•The CGG KI mouse shows reduced levels of Fmrp relative to wildtype littermates.•The CGG KI Mouse shows lower levels of activity dependent proteins Arc, Fmrp, and c-Fos relative to wildtype littermates.•Smaller increases in Fmrp and Arc after motor training are associated with impaired performance. Environmental enrichment results in increased levels of Fmrp in brain and increased dendritic complexity. The present experiment evaluated activity-dependent increases in Fmrp levels in the motor cortex in response to training on a skilled forelimb reaching task in the CGG KI mouse model of the fragile X premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot in the contralateral motor cortex of mice following training to reach for sucrose pellets with a non-preferred paw and compared to levels in the ipsilateral motor cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein levels in the contralateral compared to the ipsilateral hemisphere; however, the increase in CGG KI mice was less than wildtype mice. Increases in Fmrp and Arc proteins scaled with learning, whereas this relationship was not observed with the c-Fos levels. These data suggest the possibility that reduced levels of activity-dependent proteins associated with synaptic plasticity such as Fmrp and Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice and the fragile X premutation.