Exaggerated Cap-Dependent Translation as a Mechanism for Corticostriatal Dysfunction in Fragile X Syndrome Model Mice
Abstract
Our two laboratories Klann and Bagni - are committed to understanding the detailed molecular abnormalities associated with developmental disabilities and how these result in synaptic dysfunction and aberrant behavior. Our overall hypothesis is that repetitive and perseverative behaviors exhibited by FXS patients that can be recapitulated in the FXS model mice are caused by affected cortico-striatal synapses. To test this hypothesis, we propose two specific aims: 1) To determine cortico-striatal synaptic composition, function and plasticity in FXS model mice; 2) To determine whether altered cortico-striatal synaptic plasticity and repetitive/perseverative behaviors displayed by FXS model mice are reversed by novel cap-dependent translation inhibitors. Our specific tasks are centered on a proteomic study of FXS striatal synapses by using a transgenic mouse model that allows capturing native synapses. Purified synapse will be analyzed by mass spectrometry and the data will be validated using biochemical and cellular methods. The comparison of the synaptic proteome between the wild type and the FXS mice during development will identify which complexes are affected in FXS and possibly in other synaptopathies. These data will complement the electrophysiological and behavioral studies performed by the coordinator.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2018
- Accession Number
- AD1093661
Entities
People
- Claudia Bagni
Organizations
- University of Lausanne