基因在时空上的正确表达及精确调控对许多生物学过程，如代谢、发育，细胞增殖、分化以及多种疾病的发生都至关重要。对生物学功能的精确研究往往需要以可控的方式对基因的功能进行干预。鉴于此，我们开发并优化了一系列基于CRISPR/Cas9与ERT2耦合的药物诱导系统，并将这种系统命名为融合诱导技术（hybrid inducible technologies, HIT）。在成功开发一代HIT系统的基础上，我们进一步开发了第二代技术方案HIT2（寓意“一石二鸟”，反映了它可以同时实现药物控制的基因编辑和转录激活）。我们的HIT系统和多种已发表的药物诱导系统相比，显示了多重的优质性能。在本项目中，我们将构建Rosa位点敲进的HIT2小鼠模型，从而检验HIT2在体内环境下药物诱导的基因编辑和激活，并将它广泛应用到糖脂代谢的时空特异调控的研究中。

Dynamic expression and precise modulation of genes is critical for many biology processes, including metabolism, development, cellular proliferation, differentiation, and many diseases. And investigations of biological functions in greater precision often require controlled functional perturbations. Therefore, we developed a series of drug inducible systems based on engrafting ERT2 to CRISPR/Cas9, which we.named hybrid inducible technologies (HIT). Upon successful development of the first generation HIT systems, we further established the second generation HIT2, which meant "hitting two birds with one stone" as it can achieve simultanous drug control of gene editing and transcriptional activation. Our HIT system delivered advantageous performances when comparing with published drug inducible systems..The current project will establish Rosa knockin mouse model of HIT2 and examine its performance of drug inducible gene editing and activation in vivo. Such model will find broad utility in spatial and temporal investigation of glucose/lipid metabolism.