生物谷报道：研究人员用小鼠做实验，发现了一个与神经元传递有关的变异蛋白质，该变异能打乱大脑中突触放电的平衡。这个变异在某些患有与自闭症有关的紊乱的人身上也有，变异对小鼠学习的微妙影响也许使它们能成为研究某些形式的自闭症的模式动物。变异的蛋白质是neuroligin-3，是一个突触细胞黏合分子。带有变异的小鼠的抑制性突触传递增加，从而降低了神经元的“放电率”。Katsuhiko Tabuchi和同事说，变异小鼠与它们同笼伙伴的交互有所减少，但它们的空间记忆比没有变异的小鼠要好。研究人员指出，这与人类行为和遗传相类似，意味着抑制性突触传递的增加也许与某种形式的自闭症有关。
原始出处:
Published Online September 6, 2007
Science DOI: 10.1126/science.1146221
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@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.
