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    Precise genetic engineering in specific cell types within an intact organism is intriguing yet challenging, especially in a spatiotemporal manner without the interference caused by chemical inducers. Here we engineered a photoactivatable Dre recombinase based on the identification of an optimal split site and demonstrated that it efficiently regulated transgene expression in mouse tissues spatiotemporally upon blue light illumination. Moreover, through a double-floxed inverted open reading frame strategy, we developed a Cre-activated light-inducible Dre (CALID) system. Taking advantage of well-defined cell-type-specific promoters or a well-established Cre transgenic mouse strain, we demonstrated that the CALID system was able to activate endogenous reporter expression for either bulk or sparse labeling of CaMKII╬▒-positive excitatory neurons and parvalbumin interneurons in the brain. This flexible and tunable system could be a powerful tool for the dissection and modulation of developmental and genetic complexity in a wide range of biological systems.


    Huiying Li, Qiansen Zhang, Yiran Gu, Yingyin Wu, Yamei Wang, Liren Wang, Shijie Feng, Yaqiang Hu, Yansen Zheng, Yongmei Li, Haifeng Ye, Bin Zhou, Longnian Lin, Mingyao Liu, Huaiyu Yang, Dali Li. Efficient photoactivatable Dre recombinase for cell type-specific spatiotemporal control of genome engineering in the mouse. Proceedings of the National Academy of Sciences of the United States of America. 2020 Dec 29;117(52):33426-33435

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    PMID: 33318209

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