Expression of mutant human DISC1 in mice supports abnormalities in differentiation of oligodendrocytes.
Expression of mutant human DISC1 in mice supports abnormalities in differentiation of oligodendrocytes.
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DOI：
10.1016/j.schres.2011.04.021
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发表时间：
2011-08
影响因子：
4.5
通讯作者：
Haroutunian, Vahram
中科院分区：
文献类型：
--
作者：
Katsel, Pavel;Tan, Weilun;Abazyan, Bagrat;Davis, Kenneth L.;Ross, Christopher;Pletnikov, Mikhail V.;Haroutunian, Vahram
关键词：
少突胶质细胞（OLG）分化异常和OLG基因表达缺陷已被描述为精神分裂症（SZ）。最近的研究揭示了精神分裂症中DISC1基因在神经发育中的一个关键要求。前脑限制表达突变体人DISC1 （ΔhDISC1）的转基因小鼠表现出与SZ相似的神经解剖学和行为异常。我们试图确定ΔhDISC1的表达是否会影响该小鼠模型中OLGs的发育。研究了ΔhDISC1小鼠神经发育不同阶段（E15和P1天）和成年期前脑中OLG和细胞周期相关基因和蛋白的表达。结果表明，ΔhDISC1的表达对少突胶质细胞的分化和功能有显著影响，表现为OLG的过早分化和其祖细胞的增殖增加。其他研究结果表明，神经调节蛋白1及其受体可能是观察到的OLG基因上调的促进因素。因此，在一个模型系统中，突变体hDISC1可能会干扰OLG功能，这为研究SZ的发病机制提供了新的途径。
Abnormalities in oligodendrocyte (OLG) differentiation and OLG gene expression deficit have been described in schizophrenia (SZ). Recent studies revealed a critical requirement for Disrupted-in-Schizophrenia 1 (DISC1) in neural development. Transgenic mice with forebrain restricted expression of mutant human DISC1 (ΔhDISC1) are characterized by neuroanatomical and behavioral abnormalities reminiscent of some features of SZ. We sought to determine whether the expression of ΔhDISC1 may influence the development of OLGs in this mouse model. OLG- and cell cycle-associated gene and protein expression were characterized in the forebrain of ΔhDISC1 mice during different stages of neurodevelopment (E15 and P1 days) and in adulthood. The results suggest that the expression of ΔhDISC1 exerts a significant influence on oligodendrocyte differentiation and function, evidenced by premature OLG differentiation and increased proliferation of their progenitors. Additional findings showed that neuregulin 1 and its receptors may be contributing factors to the observed upregulation of OLG genes. Thus, OLG function may be perturbed by mutant hDISC1 in a model system that provides new avenues for studying aspects of the pathogenesis of SZ.
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影响因子：
16.2
作者：
Brinkmann, Bastian G.;Agarwal, Amit;Sereda, Michael W.;Garratt, Alistair N.;Mueller, Thomas;Wende, Hagen;Stassart, Ruth M.;Nawaz, Schanila;Humml, Christian;Velanac, Viktorija;Radyushkin, Konstantin;Goebbels, Sandra;Fischer, Tobias M.;Franklin, Robin J.;Lai, Cary;Ehrenreich, Hannelore;Birchmeier, Carmen;Schwab, Markus H.;Nave, Klaus Armin
通讯作者：
Nave, Klaus Armin
影响因子：
10.6
作者：
Bartzokis, G;Nuechterlein, KH;Mintz, J
通讯作者：
Mintz, J
影响因子：
4.5
作者：
Barley, Kevin;Dracheva, Stella;Byne, William
通讯作者：
Byne, William
影响因子：
16.2
作者：
Flames, N;Long, JE;Marín, O
通讯作者：
Marín, O
影响因子：
11
作者：
Flynn, SW;Lang, DJ;Honer, WG
通讯作者：
Honer, WG