Neuron-Specific Genome Modification in the Adult Rat Brain Using CRISPR-Cas9 Transgenic Rats

Susanne Bäck, Julie Necarsulmer, Leslie R. Whitaker, Lamarque M. Coke, Pyry Koivula, Emily J. Heathward, Lowella V. Fortuno, Yajun Zhang, C. Grace Yeh, Heather A. Baldwin, Morgan D. Spencer, Carlos A. Mejias-Aponte, James Pickel, Alexander F. Hoffman, Charles E. Spivak, Carl R. Lupica, Suzanne M. Underhill, Susan G. Amara, Andrii Domanskyi, Jenni E. AnttilaMikko Airavaara, Bruce T. Hope, F. Kent Hamra, Christopher T. Richie, Brandon K. Harvey

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Historically, the rat has been the preferred animal model for behavioral studies. Limitations in genome modification have, however, caused a lag in their use compared to the bevy of available transgenic mice. Here, we have developed several transgenic tools, including viral vectors and transgenic rats, for targeted genome modification in specific adult rat neurons using CRISPR-Cas9 technology. Starting from wild-type rats, knockout of tyrosine hydroxylase was achieved with adeno-associated viral (AAV) vectors expressing Cas9 or guide RNAs (gRNAs). We subsequently created an AAV vector for Cre-dependent gRNA expression as well as three new transgenic rat lines to specifically target CRISPR-Cas9 components to dopaminergic neurons. One rat represents the first knockin rat model made by germline gene targeting in spermatogonial stem cells. The rats described herein serve as a versatile platform for making cell-specific and sequence-specific genome modifications in the adult brain and potentially other Cre-expressing tissues of the rat. Limited availability of transgenic rats has hindered their utility in modeling human behavior and cognition. Bäck, Necarsulmer, et al. describe new transgenic rats and viral vectors that enable neuron- and region-specific gene modifications within the adult rat brain.

Original languageEnglish (US)
Pages (from-to)105-119.e8
Issue number1
StatePublished - Apr 3 2019


  • AAV
  • CRISPR-Cas9
  • MANF
  • brain
  • genome editing
  • lsl-Cas9
  • spermatogonial stem cells
  • transgenic rat

ASJC Scopus subject areas

  • Neuroscience(all)


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