Here we report the expansion of the genetic code of Mus musculus with various unnatural amino acids including Ne-acetyl-lysine. Stable integration of transgenes encoding an engineered Nϵ-acetyl-lysyl-tRNA synthetase (AcKRS)/tRNAPyl 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.
Bibliographical noteFunding Information:
This work was supported by grants from the National Research Foundation of Korea (KAIST Systems Healthcare, 2011-0020322, and 2014M3A6A4075060) to H.-S.P., and the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Science, ICT & Future Planning (2014M3A6A8066439) and Ministry of Food and Drug Safety (14182MFDS978) awarded to C.B.P.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)