Katsuhiko Tabuchi1,2,3,4,5, Jacqueline Blundell1,2,3,4,5, Mark R. Etherton1,2,3,4,5, Robert E. Hammer1,2,3,4,5, Xinran Liu1,2,3,4,5, Craig M. Powell1,2,3,4,5, Thomas C. Südhof1,2,3,4,5
1Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
2Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA
3Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
4Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
5Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Tóm tắt
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. We introduced one of these mutations into mice: the Arg
451
→Cys
451
(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 knockin mice may be a useful model for studying autism-related behaviors.
