The pogo transposable element derived with zinc finger domain ( POGZ) is one of the most frequently de novo mutated genes in patients with ASD, making POGZ a high-confidence and strong candidate ASD gene (SFARI database). However, limited studies have shown the effectiveness of oxytocin in the behavioral phenotypes in mouse models of ASD. Thus, mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. In mice, targeted disruption of genes encoding oxytocin and its receptor impairs social behavior. Recent clinical studies have suggested a potential therapeutic effect of oxytocin in ASD. Genetic variation in the oxytocin system is associated with social behavior in humans. The neuropeptide oxytocin plays a central role in social behavior. Although the prevalence rate of ASD is considerable, there are no pharmacological therapeutics for the core symptoms of ASD. Its molecular pathology is largely unclear. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.Īutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZ WT/Q1038R mice and that of WT mice. We also found that the expression level of the oxytocin receptor gene ( OXTR) was low in POGZ WT/Q1038R mice. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZ WT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZ WT/Q1038R mice. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain ( POGZ WT/Q1038R mice), showed ASD-like social behavioral deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication.
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