Dear Editor,Significant breakthrough in science often relies on the development of original tools that can perform novel functions,thus help reveal previously unknown knowledge that is not feasible to obtain using conventional tools or methods.Genetic manipulation has become a standard practice in almost all biological research fields;consequently gene expression control systems such as Cre and rtTA are indispensable tools for biomedical studies.1,2 Inducible systems of the standard gene regulation tools are controlled by addition of freely diffusible small molecules such as an antibiotic or a steroid analogue.1-3 However,the growing complexity of scientific research requires the development of more precise gene regulation systems that can spatiotemporally contrN gene expression in a tunable and reversible manner.In comparison to chemical agents,light is an ideal inducer of gene expression in a spatiotemporal specific manner.Optogenetic tools have revolutionized the studies in neuroscience and are quickly changing the standard practice in many other felds.4-9 These systems utilize light sensitive proteins to facilitate spatiotemporal protein activation,localization or genetic alterations.However,most of the light-controlled gene regulation systems were established and applied in vitro,while in vivo light switchable gene regulation system still remains a major unmet biomedical research need.A novel optogenetic mouse system that could enable spatiotemporal gene manipulations in vivo will facilitate novel discoveries.
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grants from the National Key R&D Program of China2017YFA0103500;the National Basic Research Program of China 973 Programs 2012CB518700 and 2014CB849602.We are grateful to the NIBS Animal Facility for their expert handling and care of mice,the NIBS Transgenic Animal Center for generation of knock-in mice,the NIBS Biological Resource Centre for FACS,the NIBS ima