Chunk #21 — 3. Overview of Monogenic Mouse Models of ASDs — 3.2 Post-Transcriptional Protein Modifiers or Regulators: Fmr1, Tsc1/2, Ube3a, and Pten — 3.2.1 Fmr1 (Fragile X syndrome)
subsequent dysregulated translation. For instance, the BDNF/TrkB signaling pathway converges with the mGluR5 pathway to initiate translation (reviewed in Castrén and Castrén, 2014; see Figure 1). It remains to be determined whether dysregulation of the BDNF/TrkB signaling pathway, the mGluR5 pathway, or another pathway entirely contributes to the ASD-like behaviors in FXS mouse models. There is some evidence which suggests that social deficits in mice lacking FMRP are due to decreased neuroligin1 expression and can be rescued by overexpressing neuroligin1 (Dahlhaus and El-Husseini, 2010). Additionally, mice lacking FMRP exhibit elevated postsynaptic Shank1 levels, along with a number of other synaptic proteins (Schütt et al., 2009), but more work needs to be done to confirm these results and determine whether or how these changes may lead to changes in behavior.
