Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice.
Effects of background mutations and single nucleotide polymorphisms (SNPs) on the Disc1 L100P behavioral phenotype associated with schizophrenia in mice.
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DOI：
10.1186/1744-9081-10-45
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发表时间：
2014-12-08
期刊：
影响因子：
--
通讯作者：
Akiyama K
中科院分区：
文献类型：
--
作者：
Arime Y;Fukumura R;Miura I;Mekada K;Yoshiki A;Wakana S;Gondo Y;Akiyama K
DISC 1基因是精神分裂症、双相情感障碍和抑郁症等精神疾病的潜在易感基因。已有研究报道，N-乙基-N-亚硝基脲（ENU）诱导的Disc 1基因L100 P突变小鼠表现出精神分裂症相关的行为表型。该品系最初携带C57 BL/6 J品系中的数千个ENU诱导的点突变和DBA/2 J近交系的单核苷酸多态性（SNP）。为了研究Disc 1 L100 P、背景突变和SNP对表型特征的影响，我们进行了行为分析，以更好地了解Disc 1 L100 P小鼠的表型，并使用全外显子组重测序和SNP面板进行综合遗传分析，以分别绘制ENU诱导的突变和品系特异性SNP。我们发现，在自发或甲基苯丙胺诱导的自发活动，社交或社会新奇偏好之间的Disc 1 L100 P/L100 P，L100 P/+突变体和野生型同窝仔没有差异。原始G1小鼠的全外显子组重测序鉴定了117个ENU诱导的变体，包括Disc 1 L100 P本身。2008年，将与C57 BL/6 J回交后的同源L100 P品系的2只雌性和3只雄性保藏在RIKEN BioResource Center。用DBA/2 J × C57 BL/6 J SNPs进行基因分型，发现仍有部分SNPs存在。这些结果表明，行为表型的差异的因果关系归因于存在于不同的研究组之间的Disc 1 L100 P突变小鼠线需要谨慎的调查，在进一步的研究中，考虑到其他ENU诱导的突变和/或单核苷酸多态性的影响DBA/2 J。本文的在线版本（doi：10.1186/1744-9081-10-45）包含补充材料，可供授权用户使用。
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. 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. 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. 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. 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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DOI：
10.1073/pnas.0706900104
发表时间：
2007-11-13
影响因子：
11.1
作者：
Li, Weidong;Zhou, Yu;Cannon, Tyrone D.
通讯作者：
Cannon, Tyrone D.
影响因子：
10.6
作者：
Abazyan, Bagrat;Nomura, Jun;Kannan, Geetha;Ishizuka, Koko;Tamashiro, Kellie L.;Nucifora, Frederick;Pogorelov, Vladimir;Ladenheim, Bruce;Yang, Chunxia;Krasnova, Irina N.;Cadet, Jean Lud;Pardo, Carlos;Mori, Susumu;Kamiya, Atsushi;Vogel, Michael W.;Sawa, Akira;Ross, Christopher A.;Pletnikov, Mikhail V.
通讯作者：
Pletnikov, Mikhail V.
影响因子：
6.6
作者：
Johnstone, Mandy;Thomson, Pippa A.;Porteous, David J.
通讯作者：
Porteous, David J.
DOI：
10.1073/pnas.0511189103
发表时间：
2006-03-07
影响因子：
11.1
作者：
Koike, H;Arguello, PA;Gogos, JA
通讯作者：
Gogos, JA
影响因子：
--
作者：
Cannon, TD;Hennah, W;Peltonen, L
通讯作者：
Peltonen, L