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Published Online September 6, 2007
Science DOI: 10.1126/science.1146221

Research Articles

Submitted on June 7, 2007
Accepted on August 23, 2007

A Neuroligin-3 Mutation Implicated in Autism Increases Inhibitory Synaptic Transmission in Mice

Katsuhiko Tabuchi 1, Jacqueline Blundell 2, Mark R. Etherton 1, Robert E. Hammer 3, Xinran Liu 1, Craig M. Powell 4, Thomas C. Südhof 5*

1 Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
2 Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
3 Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
4 Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
5 Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

* To whom correspondence should be addressed.
Thomas C. Südhof , E-mail: thomas.sudhof{at}utsouthwestern.edu

Autism spectrum disorders (ASDs) are characterized by impairments in social behaviors that are sometimes coupled to specialized cognitive abilities. A small percentage of ASD patients carry mutations in genes encoding neuroligins, which are postsynaptic cell adhesion molecules. Here we introduce one of these mutations into mice – the R451C-substitution in neuroligin-3. R451C-mutant mice showed impaired social interactions but enhanced spatial learning abilities. Unexpectedly, these behavioral changes were accompanied by an increase in inhibitory synaptic transmission, with no apparent effect on excitatory synapses. Deletion of neuroligin-3, in contrast, did not cause such changes, indicating that the R451C-substitution represents a gain-of-function mutation. These data suggest that increased inhibitory synaptic transmission may contribute to human ASDs and that the R451C KI mice may be a useful model for studying autism-related behaviors.


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