A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research. However, ongoing advances in genomics make genetic dissection attainable in a growing number of species. To demonstrate the potential of comparative gene editing approaches, we developed a viral-mediated CRISPR/Cas9 strategy that is predicted to target the oxytocin receptor ( Oxtr ) gene in >80 rodent species. This strategy specifically reduced OXTR levels in all evaluated species ( n = 6) without causing gross neuronal toxicity. Thus, we show that CRISPR/Cas9-based tools can function in multiple species simultaneously. Thereby, we hope to encourage comparative gene editing and improve the translatability of neuroscientific research.

中文翻译：

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针对不同啮齿动物物种的基因编辑的 AAV-CRISPR/Cas9 策略：以神经催产素受体为目标作为概念证明

神经科学的一个主要问题是动物临床前研究结果向临床结果的可转化性较差。比较神经科学可以通过研究多个物种来区分物种特异性和一般神经回路功能机制来克服这一障碍。神经回路的靶向操作通常依赖于基因解剖，并且该技术的使用仅限于少数模型物种，限制了其在比较研究中的应用。然而，基因组学的不断进步使得越来越多的物种可以进行基因解剖。为了证明比较基因编辑方法的潜力，我们开发了一种病毒介导的 CRISPR/Cas9 策略，预计该策略将靶向催产素受体（奥克斯特尔) 基因存在于超过 80 种啮齿动物物种中。该策略专门降低了所有评估物种的 OXTR 水平（n= 6) 不会引起严重的神经元毒性。因此，我们证明基于 CRISPR/Cas9 的工具可以同时在多个物种中发挥作用。因此，我们希望鼓励比较基因编辑并提高神经科学研究的可转化性。