Overview of mouse models of autism spectrum disorders.
Overview of mouse models of autism spectrum disorders.
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DOI：
10.1002/0471141755.ph0566s66
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发表时间：
2014-09-02
影响因子：
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通讯作者：
Jiang, Yong-Hui
中科院分区：
文献类型：
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作者：
Bey, Alexandra L;Jiang, Yong-Hui
本概述涵盖了许多特征明确的自闭症谱系障碍 (ASD) 小鼠模型。由于文献中有许多不同设计和描述的小鼠模型，这里提出的模型代表了基因工程模型的例子，其中人类遗传证据支持靶向突变与小鼠模型的行为表型之间的因果关系。由于自闭症谱系障碍的诊断主要基于人类的行为评估，因此我们强调不同模型中小鼠行为与人类自闭症行为的相似性。然而，由于人类自闭症谱系障碍的特征行为属于社会互动、交流和受限兴趣领域，因此在啮齿类动物中使用的各种行为测定的转化价值仍然是一个争论的话题。使用具有良好结构和表面有效性的基因工程小鼠模型将为研究潜在的病理生理机制和发现潜在的治疗干预措施提供一个平台，这些干预措施有望转化为自闭症谱系障碍的有效治疗方法。我们还说明了由于与人类自闭症谱系障碍相关的相当大的临床和分子异质性，在啮齿类动物自闭症谱系障碍建模领域中面临的几个重大挑战。
This overview covers many well-characterized mouse models of autism spectrum disorders (ASDs). As there are numerous mouse models of varying design and description in the literature, the models presented here represent examples of genetically engineered models where human genetic evidence supports a causative relationship between the targeted mutation and the behavioral phenotype of the mouse models. As the diagnosis of ASDs is primarily based on behavioral evaluations in humans, we highlight the murine behavioral analogs to human autistic behaviors in different models. However, because the characteristic behaviors of ASDs in humans are in the domains of social interaction, communication, and restricted interests, the translational value of various behavioral assays used in rodents remains a subject of debate. Using genetically engineered mouse models with good construct and face validity will provide a platform for investigating underlying pathophysiological mechanisms and discovering potential therapeutic interventions which will hopefully translate into effective treatments for ASDs. We also illustrate several significant challenges in the field of modeling ASDs in rodents due to the considerable clinical and molecular heterogeneity associated with ASDs in humans.