biostudies-literatureUnknown8Han SHere we report the expansion of the genetic code of Mus musculus with various unnatural amino acids including N^ɛ-acetyl-lysine. Stable integration of transgenes encoding an engineered N^ɛ-acetyl-lysyl-tRNA synthetase (AcKRS)/tRNA^Pyl pair into the mouse genome enables site-specific incorporation of unnatural amino acids into a target protein in response to the amber codon. We demonstrate temporal and spatial control of protein acetylation in various organs of the transgenic mouse using a recombinant green fluorescent protein (GFPuv) as a model protein. This strategy will provide a powerful tool for systematic in vivo study of cellular proteins in the most commonly used mammalian model organism for human physiology and disease.Nature communications14568https://www.ebi.ac.uk/biostudies/studies/S-EPMC5321798biostudies-literatureExpanding the genetic code of Mus musculus.PMC5321798Lee SPark HSPark CBYang AHan SLee HWfalseExpanding the genetic code of Mus musculus.Here we report the expansion of the genetic code of Mus musculus with various unnatural amino acids including N^ɛ-acetyl-lysine. Stable integration of transgenes encoding an engineered N^ɛ-acetyl-lysyl-tRNA synthetase (AcKRS)/tRNA^Pyl pair into the mouse genome enables site-specific incorporation of unnatural amino acids into a target protein in response to the amber codon. We demonstrate temporal and spatial control of protein acetylation in various organs of the transgenic mouse using a recombinant green fluorescent protein (GFPuv) as a model protein. This strategy will provide a powerful tool for systematic in vivo study of cellular proteins in the most commonly used mammalian model organism for human physiology and disease.2017-01-01T00:00:00Z2017 Feb2025-04-18T19:22:54.003Z2019-03-27T02:37:09ZS-EPMC53217982822077110.1038/ncomms14568