@article{7080f494822242f489cbe92fc596a33b,
title = "BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System",
abstract = "Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields.",
keywords = "Molecular Biology, Molecular Neuroscience, Neuroanatomy, Techniques in Neuroscience",
author = "Keigo Kohara and Akitoshi Inoue and Yousuke Nakano and Hirokazu Hirai and Takuya Kobayashi and Masato Maruyama and Ryosuke Baba and Chiho Kawashima",
note = "Funding Information: We thank Y. Tatsumi, T. Unzai, E. Oiki, K. Nitta, A. Konno, A. Onishi, and N. McCullough for their assistance with the experiments. We thank H. Matsuda for her encouragement. This research was partially supported by the program for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from the Japan Agency for Medical Research and Development , AMED under the Grant Number JP19 dm0207057 . This study was supported by Center for Medical Research and Education, Graduate School of Medicine, Osaka University , and grants from JSPS ( 16H03304 , 19H03534 , and 19K22583 ) and the Takeda Science Foundation to K.K. Funding Information: We thank Y. Tatsumi, T. Unzai, E. Oiki, K. Nitta, A. Konno, A. Onishi, and N. McCullough for their assistance with the experiments. We thank H. Matsuda for her encouragement. This research was partially supported by the program for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from the Japan Agency for Medical Research and Development, AMED under the Grant Number JP19 dm0207057. This study was supported by Center for Medical Research and Education, Graduate School of Medicine, Osaka University, and grants from JSPS (16H03304, 19H03534, and 19K22583) and the Takeda Science Foundation to K.K. K.K. conceived, designed, and performed the BATTLE-recombinase experiments. A.I. T.K. and K.K. performed the ExM experiments. H.H. packaged the lentiviruses and AAVs. K.K. and M.M. performed the viral molecular experiments. Y.N. R.B. and C.K. performed the experiments using mice. K.K, C.K. and A.I. performed quantitative analysis. K.K and A.I. wrote the manuscript. K.K. supervised the entire project. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = jun,
day = "26",
doi = "10.1016/j.isci.2020.101248",
language = "English",
volume = "23",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "6",
}