Anis Contractor, PhD, Principal Investigator

Diya Zhang, PhD, Postdoctoral Fellow
Northwestern University

FRAXA Awards:
  $17,000 in 2008 (mouse care supplement)
  $50,000 in 2006-7
  $55,000 in 2005

by Anis Contractor, 8/2008

Fragile X syndrome is the most common form of inherited human mental retardation and the single largest known genetic cause of autism. In our preliminary studies we have found that the maturation of neurons and synapses in the sensory cortex of the Fragile X mouse model is delayed. This altered synaptic maturation may result in disturbances in sensory processing, and thus be responsible for the behavioral alterations that reflect the way in which Fragile X sufferers perceive their environment.

A prevailing hypothesis posits that dysregulated group I metabotropic glutamate receptor (mGluR) signaling may underlie many of the neuronal phenotypes associated with the disease. In order to determine if reducing mGluR signaling may reverse synaptic maturation deficits, we have generated a novel mouse model in which we can inactivate the gene encoding a metabotropic glutamate receptor, mGluR5, in a temporally and spatially controlled manner on the Fragile X mouse model background. In this study we will determine whether reducing the expression of mGluR5 in the cortex of Fragile X mice reverses the aberrant synaptic development in the somatosensory cortex. Furthermore this novel mouse strain will be useful for determining whether other Fragile X related symptoms and cellular neuronal alterations can be reversed by the genetic inactivation of mGluR5.