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- Title
Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits.
- Authors
Li-Feng Jiang-Xie; Hsiao-Mei Liao; Chia-Hsiang Chen; Yuh-Tarng Chen; Shih-Yin Ho; Dai-Hua Lu; Li-Jen Lee; Horng-Huei Liou; Wen-Mei Fu; Shur-Fen Gau, Susan
- Abstract
Background As elegant structures designed for neural communication, synapses are the building bricks of our mental functions. Recently, many studies have pointed out that synaptic proteinassociated mutations may lead to dysfunctions of social cognition. Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2-/-mice to investigate their phenotypes of synaptic function and social behaviors. Methods The creation of Dlgap2-/-mice was facilitated by the recombineering-based method, Cre-loxP system and serial backcross. Reversal learning in a water T-maze was used to determine repetitive behaviors. The three-chamber approach task, resident-intruder test and tube task were performed to characterize the social behaviors of mutant mice. Cortical synaptosomal fraction, Golgi-Cox staining, whole-cell patch electrophysiology and transmission electron microscopy were all applied to investigate the function and structure of synapses in the orbitofrontal cortex (OFC) of Dlgap2-/-mice. Results Dlgap2-/-mice displayed exacerbated aggressive behaviors in the resident-intruder task, and elevated social dominance in the tube test. In addition, Dlgap2-/-mice exhibited a clear reduction of receptors and scaffold proteins in cortical synapses. Dlgap2-/-mice also demonstrated lower spine density, decreased peak amplitude of miniature excitatory postsynaptic current and ultra-structural deficits of PSD in the OFC. Conclusions Our findings clearly demonstrate that Dlgap2 plays a vital role in social behaviors and proper synaptic functions of the OFC. Moreover, these results may provide valuable insights into the neuropathology of autism.
- Subjects
AUTISM spectrum disorders; LABORATORY mice; SOCIAL perception; TRANSMISSION electron microscopy; HUMAN behavior; GENETICS
- Publication
Molecular Autism, 2014, Vol 5, Issue 1, p1
- ISSN
2040-2392
- Publication type
Article
- DOI
10.1186/2040-2392-5-32