Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6J genetic background.
Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6J genetic background.
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DOI：
10.1111/j.1601-183x.2009.00477.x
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发表时间：
2009-06
期刊：
影响因子：
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通讯作者：
Arnold SE
中科院分区：
文献类型：
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作者：
Cox MM;Tucker AM;Tang J;Talbot K;Richer DC;Yeh L;Arnold SE
Sandy小鼠在编码dysbinding -1 （Dtnbp1）的基因中存在缺失突变，导致杂合子中该蛋白减少，纯合子中缺失。因此，沙鼠可作为异常结合蛋白-1功能的动物模型。由于这种蛋白集中在突触组织中并影响递质释放，它可能影响介导行为的神经元过程。为了研究Dtnbp1突变对神经行为的影响，我们研究了C57BL/6J遗传背景下的沙地和野生型对照。三组动物在外部生理特征、感觉运动技能和焦虑样行为指标上无明显差异。然而，在开阔的田野中，纯合子动物过度活跃，似乎对最初的新环境表现出较少的适应性。在Morris水迷宫中，纯合动物在空间学习和记忆方面表现出明显的缺陷，在视觉关联学习方面表现出轻微的缺陷。除了最后提到的缺陷外，这些异常与海马功能障碍一致，在某些情况下，通过D2多巴胺受体的多巴胺能传递升高。由于在精神分裂症中发现了类似的空间学习和记忆缺陷，在海马体中发现了减少的异常结合蛋白-1，因此沙鼠也可以模拟与精神分裂症相关的认知和行为的某些方面。
Sandy mice have a deletion mutation in the gene encoding dysbindin-1, Dtnbp1, with consequent reduction of the protein in heterozygotes and its loss in homozygotes. The sandy mouse thus serves as an animal model of dysbindin-1 function. Since this protein is concentrated in synaptic tissue and affects transmitter release, it may affect neuronal processes that mediate behavior. To investigate the neurobehavioral effects of the Dtnbp1 mutation, we studied littermate sandy and wild-type controls on a C57BL/6J genetic background. The three animal groups were indistinguishable in their external physical characteristics, sensorimotor skills, and indices of anxiety-like behaviors. In the open field, however, homozygous animals were hyperactive and appeared to show less habituation to the initially novel environment. In the Morris water maze, homozygous animals displayed clear deficits in spatial learning and memory with marginal deficits in visual association learning. Apart from the last mention deficits, these abnormalities are consistent with hippocampal dysfunction and in some cases with elevated dopaminergic transmission via D2 dopamine receptors. Since similar deficits in spatial learning and memory have been found in schizophrenia, where decreased dysbindin-1 has been found in the hippocampus, the sandy mouse may also model certain aspects of cognition and behavior relevant to schizophrenia.