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Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice

Shank2 is an abundant excitatory postsynaptic scaffolding protein that has been implicated in various neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD), intellectual disability, attention-deficit/hyperactivity disorder, and schizophrenia. Shank2-mutant mice show...

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Autores principales: Yoo, Ye-Eun, Yoo, Taesun, Kang, Hyojin, Kim, Eunjoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612946/
https://www.ncbi.nlm.nih.gov/pubmed/36311025
http://dx.doi.org/10.3389/fnmol.2022.977305
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author Yoo, Ye-Eun
Yoo, Taesun
Kang, Hyojin
Kim, Eunjoon
author_facet Yoo, Ye-Eun
Yoo, Taesun
Kang, Hyojin
Kim, Eunjoon
author_sort Yoo, Ye-Eun
collection PubMed
description Shank2 is an abundant excitatory postsynaptic scaffolding protein that has been implicated in various neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD), intellectual disability, attention-deficit/hyperactivity disorder, and schizophrenia. Shank2-mutant mice show ASD-like behavioral deficits and altered synaptic and neuronal functions, but little is known about how different brain regions and gene dosages affect the transcriptomic phenotypes of these mice. Here, we performed RNA-Seq-based transcriptomic analyses of the prefrontal cortex, hippocampus, and striatum in adult Shank2 heterozygous (HT)- and homozygous (HM)-mutant mice lacking exons 6–7. The prefrontal cortical, hippocampal, and striatal regions showed distinct transcriptomic patterns associated with synapse, ribosome, mitochondria, spliceosome, and extracellular matrix (ECM). The three brain regions were also distinct in the expression of ASD-related and ASD-risk genes. These differential patterns were stronger in the prefrontal cortex where the HT transcriptome displayed increased synaptic gene expression and reverse-ASD patterns whereas the HM transcriptome showed decreased synaptic gene expression and ASD-like patterns. These results suggest brain region- and gene dosage-differential transcriptomic changes in Shank2-mutant mice.
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spelling pubmed-96129462022-10-28 Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice Yoo, Ye-Eun Yoo, Taesun Kang, Hyojin Kim, Eunjoon Front Mol Neurosci Neuroscience Shank2 is an abundant excitatory postsynaptic scaffolding protein that has been implicated in various neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD), intellectual disability, attention-deficit/hyperactivity disorder, and schizophrenia. Shank2-mutant mice show ASD-like behavioral deficits and altered synaptic and neuronal functions, but little is known about how different brain regions and gene dosages affect the transcriptomic phenotypes of these mice. Here, we performed RNA-Seq-based transcriptomic analyses of the prefrontal cortex, hippocampus, and striatum in adult Shank2 heterozygous (HT)- and homozygous (HM)-mutant mice lacking exons 6–7. The prefrontal cortical, hippocampal, and striatal regions showed distinct transcriptomic patterns associated with synapse, ribosome, mitochondria, spliceosome, and extracellular matrix (ECM). The three brain regions were also distinct in the expression of ASD-related and ASD-risk genes. These differential patterns were stronger in the prefrontal cortex where the HT transcriptome displayed increased synaptic gene expression and reverse-ASD patterns whereas the HM transcriptome showed decreased synaptic gene expression and ASD-like patterns. These results suggest brain region- and gene dosage-differential transcriptomic changes in Shank2-mutant mice. Frontiers Media S.A. 2022-10-13 /pmc/articles/PMC9612946/ /pubmed/36311025 http://dx.doi.org/10.3389/fnmol.2022.977305 Text en Copyright © 2022 Yoo, Yoo, Kang and Kim. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Yoo, Ye-Eun
Yoo, Taesun
Kang, Hyojin
Kim, Eunjoon
Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice
title Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice
title_full Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice
title_fullStr Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice
title_full_unstemmed Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice
title_short Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice
title_sort brain region and gene dosage-differential transcriptomic changes in shank2-mutant mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612946/
https://www.ncbi.nlm.nih.gov/pubmed/36311025
http://dx.doi.org/10.3389/fnmol.2022.977305
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