Songmi Han1,*, Aerin Yang2,*, Soonjang Lee1, Han-Woong Lee3, Chan Bae Park1 & Hee-Sung Park2
1 Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea. 2 Department of Chemistry, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea. 3 Department of Biochemistry, Yonsei Laboratory Animal Research Center, Yonsei University, Seoul 03722, Republic of Korea.
* These authors contributed equally to this work.
Correspondence to Chan Bae Park or Hee-Sung Park
Here we report the expansion of the genetic code of Mus musculus with various unnatural amino acids including Nε-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.