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Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice

BACKGROUND: Disrupted-in-schizophrenia 1 (DISC1) is a promising candidate susceptibility gene for psychiatric disorders, including schizophrenia, bipolar disorder and major depression. Several previous studies reported that mice with N-ethyl-N-nitrosourea (ENU)-induced L100P mutation in Disc1 showed...

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Autores principales: Arime, Yosefu, Fukumura, Ryutaro, Miura, Ikuo, Mekada, Kazuyuki, Yoshiki, Atsushi, Wakana, Shigeharu, Gondo, Yoichi, Akiyama, Kazufumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295473/
https://www.ncbi.nlm.nih.gov/pubmed/25487992
http://dx.doi.org/10.1186/1744-9081-10-45
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author Arime, Yosefu
Fukumura, Ryutaro
Miura, Ikuo
Mekada, Kazuyuki
Yoshiki, Atsushi
Wakana, Shigeharu
Gondo, Yoichi
Akiyama, Kazufumi
author_facet Arime, Yosefu
Fukumura, Ryutaro
Miura, Ikuo
Mekada, Kazuyuki
Yoshiki, Atsushi
Wakana, Shigeharu
Gondo, Yoichi
Akiyama, Kazufumi
author_sort Arime, Yosefu
collection PubMed
description BACKGROUND: Disrupted-in-schizophrenia 1 (DISC1) is a promising candidate susceptibility gene for psychiatric disorders, including schizophrenia, bipolar disorder and major depression. Several previous studies reported that mice with N-ethyl-N-nitrosourea (ENU)-induced L100P mutation in Disc1 showed some schizophrenia-related behavioral phenotypes. This line originally carried several thousands of ENU-induced point mutations in the C57BL/6 J strain and single nucleotide polymorphisms (SNPs) from the DBA/2 J inbred strain. METHODS: To investigate the effect of Disc1 L100P, background mutations and SNPs on phenotypic characterization, we performed behavioral analyses to better understand phenotypes of Disc1 L100P mice and comprehensive genetic analyses using whole-exome resequencing and SNP panels to map ENU-induced mutations and strain-specific SNPs, respectively. RESULTS: We found no differences in spontaneous or methamphetamine-induced locomotor activity, sociability or social novelty preference among Disc1 L100P/L100P, L100P/+ mutants and wild-type littermates. Whole-exome resequencing of the original G1 mouse identified 117 ENU-induced variants, including Disc1 L100P per se. Two females and three males from the congenic L100P strain after backcrossing to C57BL/6 J were deposited to RIKEN BioResource Center in 2008. We genotyped them with DBA/2 J × C57BL/6 J SNPs and found a number of the checked SNPs still remained. CONCLUSION: These results suggest that causal attribution of the discrepancy in behavioral phenotypes to the Disc1 L100P mutant mouse line existing among different research groups needs to be cautiously investigated in further study by taking into account the effect(s) of other ENU-induced mutations and/or SNPs from DBA/2 J. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1744-9081-10-45) contains supplementary material, which is available to authorized users.
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spelling pubmed-42954732015-01-16 Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice Arime, Yosefu Fukumura, Ryutaro Miura, Ikuo Mekada, Kazuyuki Yoshiki, Atsushi Wakana, Shigeharu Gondo, Yoichi Akiyama, Kazufumi Behav Brain Funct Research BACKGROUND: Disrupted-in-schizophrenia 1 (DISC1) is a promising candidate susceptibility gene for psychiatric disorders, including schizophrenia, bipolar disorder and major depression. Several previous studies reported that mice with N-ethyl-N-nitrosourea (ENU)-induced L100P mutation in Disc1 showed some schizophrenia-related behavioral phenotypes. This line originally carried several thousands of ENU-induced point mutations in the C57BL/6 J strain and single nucleotide polymorphisms (SNPs) from the DBA/2 J inbred strain. METHODS: To investigate the effect of Disc1 L100P, background mutations and SNPs on phenotypic characterization, we performed behavioral analyses to better understand phenotypes of Disc1 L100P mice and comprehensive genetic analyses using whole-exome resequencing and SNP panels to map ENU-induced mutations and strain-specific SNPs, respectively. RESULTS: We found no differences in spontaneous or methamphetamine-induced locomotor activity, sociability or social novelty preference among Disc1 L100P/L100P, L100P/+ mutants and wild-type littermates. Whole-exome resequencing of the original G1 mouse identified 117 ENU-induced variants, including Disc1 L100P per se. Two females and three males from the congenic L100P strain after backcrossing to C57BL/6 J were deposited to RIKEN BioResource Center in 2008. We genotyped them with DBA/2 J × C57BL/6 J SNPs and found a number of the checked SNPs still remained. CONCLUSION: These results suggest that causal attribution of the discrepancy in behavioral phenotypes to the Disc1 L100P mutant mouse line existing among different research groups needs to be cautiously investigated in further study by taking into account the effect(s) of other ENU-induced mutations and/or SNPs from DBA/2 J. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1744-9081-10-45) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-08 /pmc/articles/PMC4295473/ /pubmed/25487992 http://dx.doi.org/10.1186/1744-9081-10-45 Text en © Arime et al.; licensee BioMed Central. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Arime, Yosefu
Fukumura, Ryutaro
Miura, Ikuo
Mekada, Kazuyuki
Yoshiki, Atsushi
Wakana, Shigeharu
Gondo, Yoichi
Akiyama, Kazufumi
Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice
title Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice
title_full Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice
title_fullStr Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice
title_full_unstemmed Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice
title_short Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice
title_sort effects of background mutations and single nucleotide polymorphisms (snps) on the disc1 l100p behavioral phenotype associated with schizophrenia in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295473/
https://www.ncbi.nlm.nih.gov/pubmed/25487992
http://dx.doi.org/10.1186/1744-9081-10-45
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