Crawley Jacqueline N
University of California Davis MIND Institute, Sacramento, CA 95817, USA.
Neurosci Biobehav Rev. 2023 Mar;146:105053. doi: 10.1016/j.neubiorev.2023.105053. Epub 2023 Jan 20.
More than 100 single gene mutations and copy number variants convey risk for autism spectrum disorder. To understand the extent to which each mutation contributes to the trajectory of individual symptoms of autism, molecular genetics laboratories have introduced analogous mutations into the genomes of laboratory mice and other species. Over the past twenty years, behavioral neuroscientists discovered the consequences of mutations in many risk genes for autism in animal models, using assays with face validity to the diagnostic and associated behavioral symptoms of people with autism. Identified behavioral phenotypes complement electrophysiological, neuroanatomical, and biochemical outcome measures in mutant mouse models of autism. This review describes the history of phenotyping assays in genetic mouse models, to evaluate social and repetitive behaviors relevant to the primary diagnostic criteria for autism. Robust phenotypes are currently employed in translational investigations to discover effective therapeutic interventions, representing the future direction of an intensely challenging research field.
超过100种单基因突变和拷贝数变异会增加患自闭症谱系障碍的风险。为了了解每种突变对自闭症个体症状发展轨迹的影响程度，分子遗传学实验室已将类似突变引入实验小鼠和其他物种的基因组中。在过去二十年中，行为神经科学家利用对自闭症患者的诊断和相关行为症状具有表面效度的检测方法，在动物模型中发现了许多自闭症风险基因发生突变的后果。在自闭症突变小鼠模型中，已确定的行为表型补充了电生理、神经解剖学和生化结果测量。本综述描述了基因小鼠模型中表型分析的历史，以评估与自闭症主要诊断标准相关的社交和重复行为。目前，强大的表型已用于转化研究，以发现有效的治疗干预措施，代表了这个极具挑战性的研究领域的未来方向。
