Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic proteome

• DOI: 10.1073/pnas.1502258112
• Publication Date: 2015-08-12T02:09:28Z
• Authors: Bin Tang; Tingting Wang; Huida Wan; Li Han; Xiaoyan Qin; Yaoyang Zhang; Jian Wang; Chunlei Yu; Fulvia Berton; Walter Francesconi; John R. Yates; Peter W. Vanderklish; Lujian Liao
• Keywords: Fragile X Syndrome; FMR1; Proteome; Knockout mouse; Pathogenesis

Significance Fragile X syndrome (FXS) is a frequent mental disorder characterized by intellectual disability and other symptoms including autism. The disease gene-encoded protein FMRP regulates activity-dependent translation of large number mRNAs in neurons. We used quantitative mass spectrometry to systematically compare expression neocortical synaptic fractions between Fmr1 (fragile retardation 1) knockout (KO) wild-type mice during adolescence adulthood. discovered an upregulation proteins young KO but not adult ones. Many the upregulated are correlated with increased synthesis This study provides greatly expanded view protein-level changes FXS identifies previously unrecognized developmental dynamics pathogenesis.