Animal models have been the mainstay of biological and medical research. Although there are drawbacks to any research tool, we argue that mice have been under-utilized as a tool for predicting human diseases. Here we review four examples from our research group where studying the consequences of altered gene dosage in a mouse led to the discovery of previously unrecognized human syndromes: MECP2 duplication syndrome, SHANK3 duplication syndrome, CIC haploinsufficiency syndrome, and PUM1-related disorders. We also describe the clinical phenotypes of two individuals with CIC haploinsufficiency syndrome who have not been reported previously. To help bring biological insights gained from model systems a step closer to disease gene discovery, we discuss tools and resources that will facilitate this process. Moving back and forth between the lab and the clinic, between studies of mouse models and human patients, will continue to drive disease gene discovery and lead to better understanding of gene functions and disease mechanisms, laying the groundwork for future therapeutic interventions.

中文翻译：

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鼠标模型可作为发现新的神经系统疾病的工具。

动物模型一直是生物学和医学研究的主体。尽管任何研究工具都存在弊端，但我们认为小鼠未被充分利用为预测人类疾病的工具。在这里，我们回顾了我们研究小组的四个例子，这些例子研究了基因剂量改变在小鼠中导致未发现的人类综合症的发现：MECP2复制综合症，SHANK3复制综合症，CIC单倍剂量不足综合症和PUM1相关疾病。我们还描述了先前未曾报道过的两个患有CIC单倍功能不全综合征的个体的临床表型。为了使从模型系统获得的生物学见解更接近疾病基因发现，我们讨论了有助于该过程的工具和资源。