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Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice

Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this...

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Autores principales: Li, Qi, Chan, Siu Yuen, Wong, Kwun K., Wei, Ran, Leung, Yu On, Ding, Abby Y., Hui, Tomy C. K., Cheung, Charlton, Chua, Siew E., Sham, Pak C., Wu, Ed X., McAlonan, Grainne M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886156/
https://www.ncbi.nlm.nih.gov/pubmed/26826030
http://dx.doi.org/10.1007/s10519-015-9777-8
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author Li, Qi
Chan, Siu Yuen
Wong, Kwun K.
Wei, Ran
Leung, Yu On
Ding, Abby Y.
Hui, Tomy C. K.
Cheung, Charlton
Chua, Siew E.
Sham, Pak C.
Wu, Ed X.
McAlonan, Grainne M.
author_facet Li, Qi
Chan, Siu Yuen
Wong, Kwun K.
Wei, Ran
Leung, Yu On
Ding, Abby Y.
Hui, Tomy C. K.
Cheung, Charlton
Chua, Siew E.
Sham, Pak C.
Wu, Ed X.
McAlonan, Grainne M.
author_sort Li, Qi
collection PubMed
description Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more ‘sensitive’ to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10519-015-9777-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-48861562016-06-17 Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice Li, Qi Chan, Siu Yuen Wong, Kwun K. Wei, Ran Leung, Yu On Ding, Abby Y. Hui, Tomy C. K. Cheung, Charlton Chua, Siew E. Sham, Pak C. Wu, Ed X. McAlonan, Grainne M. Behav Genet Original Research Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more ‘sensitive’ to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10519-015-9777-8) contains supplementary material, which is available to authorized users. Springer US 2016-01-29 2016 /pmc/articles/PMC4886156/ /pubmed/26826030 http://dx.doi.org/10.1007/s10519-015-9777-8 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Li, Qi
Chan, Siu Yuen
Wong, Kwun K.
Wei, Ran
Leung, Yu On
Ding, Abby Y.
Hui, Tomy C. K.
Cheung, Charlton
Chua, Siew E.
Sham, Pak C.
Wu, Ed X.
McAlonan, Grainne M.
Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice
title Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice
title_full Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice
title_fullStr Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice
title_full_unstemmed Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice
title_short Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice
title_sort tspyl2 loss-of-function causes neurodevelopmental brain and behavior abnormalities in mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886156/
https://www.ncbi.nlm.nih.gov/pubmed/26826030
http://dx.doi.org/10.1007/s10519-015-9777-8
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