Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals

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Cell-specific CRISPR/Cas9 in the adult rat brain.

Microscopic images of the midbrain of a transgenic rat that selectively expresses Cas9 in dopamine neurons. On the left side, control gRNAs were delivered to cells in the midbrain using a virus (green). On the right side, gRNAs to a target gene (white) is expressed in both dopaminergic neurons (red) and non-dopaminergic neurons. Arrows identify dopaminergic cells that received gRNAs. Only on the right side which received gRNAs to target (white) do we see the selective loss of target gene expression from dopaminergic neurons. Modified from Bäck, Necarsulmer et al Neuron 2019 with permission from Elsevier.

Publication Information

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

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

In: Neuron, vol. 102, no. 1, pp. 105–119, 2019, ISSN: 1097-4199 (Electronic); 0896-6273 (Linking).

Abstract | Links

@article{Back:2019aac,

title = {Neuron-Specific Genome Modification in the Adult Rat Brain Using CRISPR-Cas9 Transgenic Rats.},

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

url = {https://www.ncbi.nlm.nih.gov/pubmed/30792150},

doi = {10.1016/j.neuron.2019.01.035},

issn = {1097-4199 (Electronic); 0896-6273 (Linking)},

year  = {2019},

date = {2019-04-03},

urldate = {2019-04-03},

journal = {Neuron},

volume = {102},

number = {1},

pages = {105--119},

address = {Molecular Mechanisms of Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}