Heritable expansion of the genetic code in mouse and zebrafish
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Dear Editor,The genetic code can be expanded to encode unnatural amino acids (Uaas) by introducing an orthogonal tRNA/aminoacyl-tRNA synthetase (aaRS) pair to decode a stop codon.Initially developed in Escherichia coli ”1”,this strategy has been proven generally applicable in eukaryotic cells ”2” and in generating transgenic invertebrates capable of Uaa incorporation,including Caenorhabditis elegans ”3” and Drosophila melanogaster ”4”.Although cells and tissues of mouse can be transduced transiently to incorporate Uaas ”5”,it remains unknown whether transgenic vertebrates with a heritable expanded genetic code system-wide can be generated,as it is unclear whether the biological complexity of vertebrates allows the introduction,maintenance and transmission of the newly introduced genetic material for code expansion.Here we for the first time report the generation of transgenic mice and zebrafish with an expanded genetic code,providing valuable vertebrate model animals for biological and biomedical research.
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This work was supported the State Key Development Programs of China 2012CB910400 to ML,the National Natural Science Foundation of China 31371455 and 31171318 to DL,81330049 to ML,and 31528007 to SY and CY,and the Science and Technology Commission of Shanghai Municipality 14140900300 to DL.Other financial supports were provided by the ECNU Fund short-term visiting fellowship to YC,the Chinese Scholars Council CSC fellowship to MT,the Agence Nationale de la Recherche of France ANR-JCJC ChemProbe to SY and US National Institutes of Health 1R01GM118384-01 to LW.