| Literature DB >> 30792150 |
Susanne Bäck1, Julie Necarsulmer2, Leslie R Whitaker3, Lamarque M Coke1, Pyry Koivula1, Emily J Heathward2, Lowella V Fortuno2, Yajun Zhang2, C Grace Yeh3, Heather A Baldwin1, Morgan D Spencer1, Carlos A Mejias-Aponte4, James Pickel5, Alexander F Hoffman6, Charles E Spivak6, Carl R Lupica6, Suzanne M Underhill7, Susan G Amara7, Andrii Domanskyi8, Jenni E Anttila8, Mikko Airavaara8, Bruce T Hope3, F Kent Hamra9, Christopher T Richie2, Brandon K Harvey10.
Abstract
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. Published by Elsevier Inc.Entities:
Keywords: AAV; CRISPR-Cas9; MANF; brain; genome editing; lsl-Cas9; spermatogonial stem cells; transgenic rat
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Year: 2019 PMID： 30792150 DOI： 10.1016/j.neuron.2019.01.035
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173