Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.

Recent meta-analyses of schizophrenia genome-wide association studies (GWASs) have identified the CUB and SUSHI multiple domains 1 (CSMD1) gene as a statistically strong risk factor. CSMD1 is a complement control-related protein suggested to inhibit the classical complement pathway, being expressed...

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Autores principales:	Vidar M Steen, Chirag Nepal, Kari M Ersland, Rita Holdhus, Marianne Nævdal, Siri M Ratvik, Silje Skrede, Bjarte Håvik
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d88e54d129544816924ae23e36500782
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spelling	oai:doaj.org-article:d88e54d129544816924ae23e365007822021-11-18T08:46:30ZNeuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.1932-620310.1371/journal.pone.0079501https://doaj.org/article/d88e54d129544816924ae23e365007822013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244513/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Recent meta-analyses of schizophrenia genome-wide association studies (GWASs) have identified the CUB and SUSHI multiple domains 1 (CSMD1) gene as a statistically strong risk factor. CSMD1 is a complement control-related protein suggested to inhibit the classical complement pathway, being expressed in developing neurons. However, expression of CSMD1 is largely uncharacterized and relevance for behavioral phenotypes is not previously demonstrated. Here, we assess neuropsychological behaviors of a Csmd1 knockout (KO) mouse in a selection of standard behavioral tests. Deregulation of neuropsychological responses were observed in both the open field and the elevated plus maze tests, in which KO mice spent 55% and 33% less time than WT littermate mice in open areas, respectively. Altered behaviors were also observed in tail suspension and to higher acoustic stimuli, for which Csmd1 KO mice showed helplessness and moderate increase in startle amplitude, respectively. Furthermore, Csmd1 KO mice also displayed increased weight-gain and glucose tolerance, similar to a major phenotype of the metabolic syndrome that also has been associated to the human CSMD1 locus. Consistent with a role in the control of behaviors, Csmd1 was found highly expressed in the central nervous system (CNS), and with some expression in visceral fat and ovary, under tissue-specific control by a novel promoter-associated lncRNA. In summary, disruption of Csmd1 induces behaviors reminiscent of blunted emotional responses, anxiety and depression. These observations suggest an influence of the CSMD1 schizophrenia susceptibility gene on psychopathology and endophenotypes of the negative symptom spectra.Vidar M SteenChirag NepalKari M ErslandRita HoldhusMarianne NævdalSiri M RatvikSilje SkredeBjarte HåvikPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79501 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vidar M Steen Chirag Nepal Kari M Ersland Rita Holdhus Marianne Nævdal Siri M Ratvik Silje Skrede Bjarte Håvik Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.
description	Recent meta-analyses of schizophrenia genome-wide association studies (GWASs) have identified the CUB and SUSHI multiple domains 1 (CSMD1) gene as a statistically strong risk factor. CSMD1 is a complement control-related protein suggested to inhibit the classical complement pathway, being expressed in developing neurons. However, expression of CSMD1 is largely uncharacterized and relevance for behavioral phenotypes is not previously demonstrated. Here, we assess neuropsychological behaviors of a Csmd1 knockout (KO) mouse in a selection of standard behavioral tests. Deregulation of neuropsychological responses were observed in both the open field and the elevated plus maze tests, in which KO mice spent 55% and 33% less time than WT littermate mice in open areas, respectively. Altered behaviors were also observed in tail suspension and to higher acoustic stimuli, for which Csmd1 KO mice showed helplessness and moderate increase in startle amplitude, respectively. Furthermore, Csmd1 KO mice also displayed increased weight-gain and glucose tolerance, similar to a major phenotype of the metabolic syndrome that also has been associated to the human CSMD1 locus. Consistent with a role in the control of behaviors, Csmd1 was found highly expressed in the central nervous system (CNS), and with some expression in visceral fat and ovary, under tissue-specific control by a novel promoter-associated lncRNA. In summary, disruption of Csmd1 induces behaviors reminiscent of blunted emotional responses, anxiety and depression. These observations suggest an influence of the CSMD1 schizophrenia susceptibility gene on psychopathology and endophenotypes of the negative symptom spectra.
format	article
author	Vidar M Steen Chirag Nepal Kari M Ersland Rita Holdhus Marianne Nævdal Siri M Ratvik Silje Skrede Bjarte Håvik
author_facet	Vidar M Steen Chirag Nepal Kari M Ersland Rita Holdhus Marianne Nævdal Siri M Ratvik Silje Skrede Bjarte Håvik
author_sort	Vidar M Steen
title	Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.
title_short	Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.
title_full	Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.
title_fullStr	Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.
title_full_unstemmed	Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.
title_sort	neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene csmd1.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d88e54d129544816924ae23e36500782
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Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1.

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