Fragile X syndrome (FXS) and tuberous sclerosis complex (TSC) are both associated with autism and intellectual disability, and are both caused by mutations that disrupt synaptic protein synthesis. However, a recent study by Auerbach et al. found that the two diseases are caused by an opposing mechanism. Previous work showed that mutant phenotypes in Fmr1−/y mice, a model of FXS, are minimised by reducing signalling by mGluR5 (a receptor for the excitatory neurotransmitter glutamate). Conversely, the new study showed that, in Tsc2+/− mice (a model of TSC), the same effect was achieved by potentiating mGluR5 signalling. Furthermore, crossing Fmr1−/y and Tsc2+/− mice produced a strain that is indistinguishable from wild type with regards to hippocampus-dependent synaptic plasticity and cognitive function, as the mutations cancelled one another out. These results expand knowledge about synaptic defects causing FXS and TSC, and highlight the fact that information on the underlying disease mechanisms is required to provide appropriate treatment.
- Written by editorial staff. © 2012. Published by The Company of Biologists Ltd.
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