Chunk #22 — 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)
Compared to other models, little work has been published utilizing Fmr1 conditional knockout mice to determine the cell types and brain regions underlying the ASD-like phenotypes involved in FMRP dysfunction. One group reported that deletion of Fmr1 in a subset of mature neurons in cortex and hippocampus (Nse-Cre) has no effect on ASD-like behaviors (Amiri et al., 2014), whereas previous work demonstrated that deletion of another ASD susceptibility gene (Pten; see section 3.2.3) using the same Cre line produces ASD-like phenotypes (Kwon et al., 2006a). This finding is somewhat surprising, given that PTEN expression is typically suppressed in FXS, indicating some mechanistic overlap between FXS and PTEN-related ASD (Hagerman et al., 2010). There is some evidence to suggest that, similar to Mecp2 mutant mice, Fmr1 knockout mice have deficits in GABAergic signaling (GABAB reviewed in Braat and Kooy, 2014; GABAA reviewed in Braat and Kooy, 2015), but so far this has not been directly linked to behavior. Clearly, more work needs to be done to determine cell types and brain regions involved in the ASD-like features observed in FXS mouse models.
