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Assessment of Behaviors Modeling Aspects of Schizophrenia in Csmd1 Mutant Mice

Schizophrenia is a debilitating psychotic disorder that affects up to 1.5% of the population worldwide. Two recent studies in humans identified genome-wide significant associations between schizophrenia and single-nucleotide polymorphisms (SNPs) in an intron of CSMD1. The effect of deleting CSMD1 on...

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Autores principales: Distler, Margaret G., Opal, Mark D., Dulawa, Stephanie C., Palmer, Abraham A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524225/
https://www.ncbi.nlm.nih.gov/pubmed/23284669
http://dx.doi.org/10.1371/journal.pone.0051235
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author Distler, Margaret G.
Opal, Mark D.
Dulawa, Stephanie C.
Palmer, Abraham A.
author_facet Distler, Margaret G.
Opal, Mark D.
Dulawa, Stephanie C.
Palmer, Abraham A.
author_sort Distler, Margaret G.
collection PubMed
description Schizophrenia is a debilitating psychotic disorder that affects up to 1.5% of the population worldwide. Two recent studies in humans identified genome-wide significant associations between schizophrenia and single-nucleotide polymorphisms (SNPs) in an intron of CSMD1. The effect of deleting CSMD1 on mouse behavior is unknown. The present study utilized mice with a mutant Csmd1 allele in which the first exon had been ablated (KO mice). All Csmd1 transcripts that included the first exon were absent in the brains of KO mice, but there was persistent expression of at least one other transcript that does not include the first exon. Wild type (WT), heterozygous (HET), and KO mice were assessed using several well-established behavioral paradigms that model aspects of schizophrenia. Csmd1 KO mice did not differ from wild-type littermates for sensorimotor gating (measured as prepulse inhibition), social interaction, anhedonia (measured by sucrose preference), or sensitivity to the locomotor stimulant effects of the dopaminergic agent d-amphetamine. These data demonstrate that loss of Csmd1 transcripts that include the first exon does not alter multiple well-established behaviors that model aspects of schizophrenia. The SNP most strongly associated with schizophrenia in humans is between exons 3 and 4; therefore, ablation of exon 1 appeared to be a logical animal model. Nevertheless, future studies should consider alternative mouse models including gain-of-function mutations, and loss-of-function mutations that target alternative transcripts of Csmd1.
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spelling pubmed-35242252013-01-02 Assessment of Behaviors Modeling Aspects of Schizophrenia in Csmd1 Mutant Mice Distler, Margaret G. Opal, Mark D. Dulawa, Stephanie C. Palmer, Abraham A. PLoS One Research Article Schizophrenia is a debilitating psychotic disorder that affects up to 1.5% of the population worldwide. Two recent studies in humans identified genome-wide significant associations between schizophrenia and single-nucleotide polymorphisms (SNPs) in an intron of CSMD1. The effect of deleting CSMD1 on mouse behavior is unknown. The present study utilized mice with a mutant Csmd1 allele in which the first exon had been ablated (KO mice). All Csmd1 transcripts that included the first exon were absent in the brains of KO mice, but there was persistent expression of at least one other transcript that does not include the first exon. Wild type (WT), heterozygous (HET), and KO mice were assessed using several well-established behavioral paradigms that model aspects of schizophrenia. Csmd1 KO mice did not differ from wild-type littermates for sensorimotor gating (measured as prepulse inhibition), social interaction, anhedonia (measured by sucrose preference), or sensitivity to the locomotor stimulant effects of the dopaminergic agent d-amphetamine. These data demonstrate that loss of Csmd1 transcripts that include the first exon does not alter multiple well-established behaviors that model aspects of schizophrenia. The SNP most strongly associated with schizophrenia in humans is between exons 3 and 4; therefore, ablation of exon 1 appeared to be a logical animal model. Nevertheless, future studies should consider alternative mouse models including gain-of-function mutations, and loss-of-function mutations that target alternative transcripts of Csmd1. Public Library of Science 2012-12-17 /pmc/articles/PMC3524225/ /pubmed/23284669 http://dx.doi.org/10.1371/journal.pone.0051235 Text en © 2012 Distler et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Distler, Margaret G.
Opal, Mark D.
Dulawa, Stephanie C.
Palmer, Abraham A.
Assessment of Behaviors Modeling Aspects of Schizophrenia in Csmd1 Mutant Mice
title Assessment of Behaviors Modeling Aspects of Schizophrenia in Csmd1 Mutant Mice
title_full Assessment of Behaviors Modeling Aspects of Schizophrenia in Csmd1 Mutant Mice
title_fullStr Assessment of Behaviors Modeling Aspects of Schizophrenia in Csmd1 Mutant Mice
title_full_unstemmed Assessment of Behaviors Modeling Aspects of Schizophrenia in Csmd1 Mutant Mice
title_short Assessment of Behaviors Modeling Aspects of Schizophrenia in Csmd1 Mutant Mice
title_sort assessment of behaviors modeling aspects of schizophrenia in csmd1 mutant mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524225/
https://www.ncbi.nlm.nih.gov/pubmed/23284669
http://dx.doi.org/10.1371/journal.pone.0051235
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