Hippocampal gamma and sharp-wave ripple oscillations are altered in a Cntnap2 mouse model of autism spectrum disorder

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. 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 (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. 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.

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Behavioral phenotypes and neurobiological mechanisms in the Shank1 mouse model for autism spectrum disorder: A translational perspective

Behavioural Brain Research ◽

10.1016/j.bbr.2017.09.038 ◽

2018 ◽

Vol 352 ◽

pp. 46-61 ◽

Cited By ~ 12

Author(s):

A. Özge Sungur ◽

Rainer K.W. Schwarting ◽

Markus Wöhr

Keyword(s):

Autism Spectrum Disorder ◽

Mouse Model ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Behavioral Phenotypes

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High Resolution Magnetic Resonance Imaging for Characterization of the Neuroligin-3 Knock-in Mouse Model Associated with Autism Spectrum Disorder

PLoS ONE ◽

10.1371/journal.pone.0109872 ◽

2014 ◽

Vol 9 (10) ◽

pp. e109872 ◽

Cited By ~ 18

Author(s):

Manoj Kumar ◽

Jeffery T. Duda ◽

Wei-Ting Hwang ◽

Charles Kenworthy ◽

Ranjit Ittyerah ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Autism Spectrum Disorder ◽

Magnetic Resonance ◽

High Resolution ◽

Mouse Model ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Resonance Imaging

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Mouse Model Systems of Autism Spectrum Disorder: Replicability and Informatics Signature

10.1101/561233 ◽

2019 ◽

Author(s):

Patricia Kabitzke ◽

Diana Morales ◽

Dansha He ◽

Kimberly Cox ◽

Jane Sutphen ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Social Behavior ◽

Mouse Model ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Model Systems ◽

Activity Levels ◽

Phenotypic Differences ◽

Genetic Mouse Model ◽

Unitary Concept

3.AbstractBackgroundPhenotyping mouse model systems of human disease has proven to be a difficult task, with frequent poor inter- and intra-laboratory replicability and translatability, particularly in behavioral domains such as social and verbal function. However, establishing robust animal model systems with strong construct validity is of fundamental importance as they are central tools for understanding disease pathophysiology and developing therapeutics. To complete our studies of mouse model systems relevant to autism spectrum disorder (ASD), we present a replication of the main findings from our two published studies comprising five genetic mouse model systems of ASD.MethodsTo assess the robustness of our previous results, we chose the two model systems that showed the greatest phenotypic differences, the Shank3/F and Cntnap2, and repeated assessments of general health, activity, and social behavior. We additionally explored all five model systems in the same framework, comparing all results obtained in this three-yearlong effort using informatics techniques to look for commonalities and differences.ResultsResults in the current study were very similar to our previously published results. The informatics signatures of the two model systems chosen for the replication showed that they were most distinguished by activity levels. Although the two model systems were opposite in this regard, those aspects of their social behavior not confounded by activity (vocalizations) were similar.ConclusionsOur results showed high intra-laboratory replicability of results, even for those with effect sizes that were not particularly large, suggesting that discrepancies in the literature may be dependent on subtle differences in testing conditions, housing enrichment, or background strains and not so much on the variability of the behavioral phenotypes. The overall informatics analysis suggests two main classes of model systems that in some aspects lie on opposite ends of the behavioral spectrum, supporting the view that autism is not a unitary concept.

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