Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes

Abstract PTEN has a strong Mendelian association with autism spectrum disorder (ASD), representing a special case in autism’s complex genetic architecture. Animal modeling for constitutional Pten mutation creates an opportunity to study how disruption of Pten affects neurobiology and glean potential...

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Autores principales:	Stetson Thacker, Charis Eng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/27a1671a0c874649a0fa9e2d133d2d64
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spelling	oai:doaj.org-article:27a1671a0c874649a0fa9e2d133d2d642021-12-02T18:25:06ZTranscriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes10.1038/s41525-021-00201-z2056-7944https://doaj.org/article/27a1671a0c874649a0fa9e2d133d2d642021-06-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00201-zhttps://doaj.org/toc/2056-7944Abstract PTEN has a strong Mendelian association with autism spectrum disorder (ASD), representing a special case in autism’s complex genetic architecture. Animal modeling for constitutional Pten mutation creates an opportunity to study how disruption of Pten affects neurobiology and glean potential insight into ASD pathogenesis. Subsequently, we comprehensively characterized the neural (phospho)proteome of Pten m3m4/m3m4 mice, which exhibits cytoplasmic-predominant Pten expression, by applying mass spectrometry technology to their brains at two-weeks- (P14) and six-weeks-of-age (P40). The differentially expressed/phosphorylated proteins were subjected to gene enrichment, pathway, and network analyses to assess the affected biology. We identified numerous differentially expressed/phosphorylated proteins, finding greater dysregulation at P40 consistent with prior transcriptomic data. The affected pathways were largely related to PTEN function or neurological processes, while scant direct overlap was found across datasets. Network analysis pointed to ASD risk genes like Pten and Psd-95 as major regulatory hubs, suggesting they likely contribute to initiation or maintenance of cellular and perhaps organismal phenotypes related to ASD.Stetson ThackerCharis EngNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Stetson Thacker Charis Eng Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes
description	Abstract PTEN has a strong Mendelian association with autism spectrum disorder (ASD), representing a special case in autism’s complex genetic architecture. Animal modeling for constitutional Pten mutation creates an opportunity to study how disruption of Pten affects neurobiology and glean potential insight into ASD pathogenesis. Subsequently, we comprehensively characterized the neural (phospho)proteome of Pten m3m4/m3m4 mice, which exhibits cytoplasmic-predominant Pten expression, by applying mass spectrometry technology to their brains at two-weeks- (P14) and six-weeks-of-age (P40). The differentially expressed/phosphorylated proteins were subjected to gene enrichment, pathway, and network analyses to assess the affected biology. We identified numerous differentially expressed/phosphorylated proteins, finding greater dysregulation at P40 consistent with prior transcriptomic data. The affected pathways were largely related to PTEN function or neurological processes, while scant direct overlap was found across datasets. Network analysis pointed to ASD risk genes like Pten and Psd-95 as major regulatory hubs, suggesting they likely contribute to initiation or maintenance of cellular and perhaps organismal phenotypes related to ASD.
format	article
author	Stetson Thacker Charis Eng
author_facet	Stetson Thacker Charis Eng
author_sort	Stetson Thacker
title	Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes
title_short	Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes
title_full	Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes
title_fullStr	Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes
title_full_unstemmed	Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes
title_sort	transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant pten expression with autism-like phenotypes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/27a1671a0c874649a0fa9e2d133d2d64
work_keys_str_mv	AT stetsonthacker transcriptomephosphoproteomecharacterizationofbrainofagermlinemodelofcytoplasmicpredominantptenexpressionwithautismlikephenotypes AT chariseng transcriptomephosphoproteomecharacterizationofbrainofagermlinemodelofcytoplasmicpredominantptenexpressionwithautismlikephenotypes
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Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes

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