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Biomol Ther (Seoul). 2017 Jul 1;25(4):374-382. doi: 10.4062/biomolther.2016.242.

Sex Differences in Autism-Like Behavioral Phenotypes and Postsynaptic Receptors Expression in the Prefrontal Cortex of TERT Transgenic Mice.

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Center for Neuroscience Research, SMART Institute of Advanced Biomedical Sciences, Konkuk University, Seoul 05029, Republic of Korea.
College of Human Ecology, Cornell University, Ithaca, New York 14853, United States of America.
Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Neuropsychiatry, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.


Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates. Along these differences are the male-specific increased expressions of postsynaptic proteins which are the NMDA and AMPA receptors in the prefrontal cortex. The vGluT1 presynaptic proteins, but not GAD, were upregulated in both sexes of TERT-tg mice, although it is more significantly pronounced in the male group. Here, we confirmed that the behavioral effect of TERT overexpression in mice was male-specific, suggesting that the aberration of this gene and its downstream pathways preferentially affect the functional development of the male brain, consistent with the male preponderance in ASD.


Autism spectrum disorder; Excitatory/Inhibitory imbalance; Sex difference; Synapse; TERT transgenic mice

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