Early communication deficits in theShank1knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context

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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Exploring Growth in Expressive Communication of Infants and Toddlers With Autism Spectrum Disorder

Journal of Early Intervention ◽

10.1177/1053815121995578 ◽

2021 ◽

pp. 105381512199557

Author(s):

Jay Buzhardt ◽

Anna Wallisch ◽

Dwight Irvin ◽

Brian Boyd ◽

Brenda Salley ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Progress Monitoring ◽

Autism Spectrum ◽

Growth Patterns ◽

Spectrum Disorder ◽

Future Research ◽

Infants And Toddlers ◽

Early Communication ◽

Children With Asd ◽

Language Growth

One of the earliest indicators of autism spectrum disorder (ASD) is delay in language and social communication. Despite consensus on the benefits of earlier diagnosis and intervention, our understanding of the language growth of children with ASD during the first years of life remains limited. Therefore, this study compared communication growth patterns of infants and toddlers with ASD to growth benchmarks of a standardized language assessment. We conducted a retrospective analysis of growth on the Early Communication Indicator (ECI) of 23 infants and toddlers who received an ASD diagnosis in the future. At 42 months of age, children with ASD had significantly lower rates of gestures, single words, and multiple words, but significantly higher rates of nonword vocalizations. Children with ASD had significantly slower growth of single and multiple words, but their rate of vocalization growth was significantly greater than benchmark. Although more research is needed with larger samples, because the ECI was designed for practitioners to monitor children’s response to intervention over time, these findings show promise for the ECI’s use as a progress monitoring measure for young children with ASD. Limitations and the need for future research are discussed.

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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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Acquisition of Verb Meaning From Syntactic Distribution in Preschoolers With Autism Spectrum Disorder

Language Speech and Hearing Services in Schools ◽

10.1044/2018_lshss-stlt1-17-0126 ◽

2018 ◽

Vol 49 (3S) ◽

pp. 668-680 ◽

Cited By ~ 7

Author(s):

Sabrina Horvath ◽

Elizabeth McDermott ◽

Kathleen Reilly ◽

Sudha Arunachalam

Keyword(s):

Autism Spectrum Disorder ◽

Social Context ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Future Research ◽

The Novel ◽

Prior Work ◽

Verb Learning ◽

Children With Asd ◽

Syntactic Frames

Purpose Our goal was to investigate whether preschool children with autism spectrum disorder (ASD) can begin to learn new word meanings by attending to the linguistic contexts in which they occur, even in the absence of visual or social context. We focused on verbs because of their importance for subsequent language development. Method Thirty-two children with ASD, ages 2;1–4;5 (years;months), participated in a verb-learning task. In a between-subjects design, they were randomly assigned to hear novel verbs in either transitive or intransitive syntactic frames while watching an unrelated silent animation or playing quietly with a toy. In an eye-tracking test, they viewed two video scenes, one depicting a causative event (e.g., boy spinning girl) and the other depicting synchronous events (e.g., boy and girl waving). They were prompted to find the referents of the novel verbs, and their eye gaze was measured. Results Like typically developing children in prior work, children with ASD who had heard the verbs in transitive syntactic frames preferred to look to the causative scene as compared to children who had heard intransitive frames. Conclusions This finding replicates and extends prior work on verb learning in children with ASD by demonstrating that they can attend to a novel verb's syntactic distribution absent relevant visual or social context, and they can use this information to assign the novel verb an appropriate meaning. We discuss points for future research, including examining individual differences that may impact success and contrasting social and nonsocial word-learning tasks directly.

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