Neuron — Dölen et al.

New report: Potential relief for Fragile X sufferers.

Fragile X can be simulated in a mouse if you knock out a gene (FMR1). If you further block a receptor — called mGlu5 (metabotropic glutamate receptor 5 or MGR5) — the behavioral symptoms can altered. In the mouse model, the could genetically delete 50% of the mGlu5 receptors, but there are molecules which are known blockers to do the same thing. (Here’s also an article from Nature News.) I think this is huge news — but my bias is that the trinucleotide repeats (like those found in Fragile X) are responsible for many, many more behavioral afflictions than we know. Full abstract after the jump:

Copyright © 2007 Cell Press. All rights reserved.
Neuron, Vol 56, 955-962, 20 December 2007

Report

Correction of Fragile X Syndrome in Mice

Gül Dölen,¹,² Emily Osterweil,¹ B.S. Shankaranarayana Rao,³ Gordon B. Smith,¹ Benjamin D. Auerbach,¹ Sumantra Chattarji,⁴ and Mark F. Bear¹,

¹ Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
² Department of Neuroscience, Brown Medical School and the Division of Biology and Medicine, Providence, RI 02912, USA
³ Department of Neurophysiology, National Institute of Mental Health and Neuroscience, Bangalore 560 002, India
⁴ National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560 002, India

Corresponding author
Mark F. Bear
mbear@mit.edu

Fragile X syndrome (FXS) is the most common form of heritable mental retardation and the leading identified cause of autism. FXS is caused by transcriptional silencing of the FMR1 gene that encodes the fragile X mental retardation protein (FMRP), but the pathogenesis of the disease is unknown. According to one proposal, many psychiatric and neurological symptoms of FXS result from unchecked activation of mGluR5, a metabotropic glutamate receptor. To test this idea we generated Fmr1 mutant mice with a 50% reduction in mGluR5 expression and studied a range of phenotypes with relevance to the human disorder. Our results demonstrate that mGluR5 contributes significantly to the pathogenesis of the disease, a finding that has significant therapeutic implications for fragile X and related developmental disorders.