ArticleNeuron2019
Neuron-Specific Genome Modification in the Adult Rat Brain Using CRISPR-Cas9 Transgenic Rats.
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Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59 citing papers in PubMed.
- Top-down control of the descending pain modulatory system drives multimodal placebo analgesia.Neuron · 2026Article
- Kappa opioid receptors in excitatory spinal neurons gate acute pain: evidence from mouse and human.bioRxiv : the preprint server for biology · 2026Article
- Transcranial Calcium Macro-Imaging From the Auditory Cortex of Thy1-Cre-Driven GCaMP8 Transgenic Rats.Neuropsychopharmacology reports · 2026Article
- Sex-specific organization and synaptic signaling in prefrontal-hypothalamic circuitry.bioRxiv : the preprint server for biology · 2026Article
- Response dynamics of discrete subiculum→retrosplenial cortex projections underlying trace fear conditioning.iScience · 2026Article
- Distinguishing Pseudotransduction and True Transduction Enables Characterization and Bioengineering of Extracellular Vesicle-Adeno-Associated Virus Vectors.Journal of extracellular vesicles · 2026Article
- Generation and characterization of a tamoxifen-inducible, Cre driver rat for transgene expression in microglia.Scientific reports · 2025Article
- Chemoarchitectural studies of the rat hypothalamus and zona incerta.bioRxiv : the preprint server for biology · 2025Article
- Generation and characterization of a tamoxifen-inducible, Cre driver rat for transgene expression in microglia.Research square · 2025Article
- Rat somatic genome editing enables ER+ breast cancer modeling.bioRxiv : the preprint server for biology · 2025Article
- SWITCHER, a CRISPR-inducible floxed wild-type Cre regulating CRISPR activity.Communications biology · 2025Article
- The mouse posterior insular cortex encodes expressive and receptive aspects of courtship vocalizations.Cell reports · 2025Article
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- Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits.bioRxiv : the preprint server for biology · 2025Article
- A brief guide for gene delivery to the brain using adeno-associated viral vectors.Molecules and cells · 2025Review
- SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head.Molecular medicine (Cambridge, Mass.) · 2024Article
- Versatile Cell Penetrating Peptide for Multimodal CRISPR Gene Editing in Primary Stem Cells.bioRxiv : the preprint server for biology · 2024Article
- CRISPR/Cas9-mediated neuronal deletion of 5-lipoxygenase alleviates deficits in mouse models of epilepsy.Journal of advanced research · 2024Article
- Article
- Rat Models of Hormone Receptor-Positive Breast Cancer.Journal of mammary gland biology and neoplasia · 2024Review
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Authors and funding
25 authors.
Susanne BäckMolecular Mechanisms of Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Julie NecarsulmerOptogenetics and Transgenic Technology Core/Genetic Engineering and Viral Vector Core, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Leslie R WhitakerNeuronal Ensembles in Drug Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Lamarque M CokeMolecular Mechanisms of Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Pyry KoivulaMolecular Mechanisms of Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Emily J HeathwardOptogenetics and Transgenic Technology Core/Genetic Engineering and Viral Vector Core, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Lowella V FortunoOptogenetics and Transgenic Technology Core/Genetic Engineering and Viral Vector Core, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Yajun ZhangOptogenetics and Transgenic Technology Core/Genetic Engineering and Viral Vector Core, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
C Grace YehNeuronal Ensembles in Drug Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Heather A BaldwinMolecular Mechanisms of Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Morgan D SpencerMolecular Mechanisms of Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Carlos A Mejias-AponteHistology Core, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
James PickelTransgenic Technology Core, Intramural Research Program, National Institute of Mental Health, Bethesda, MD 20892, USA.
Alexander F HoffmanElectrophysiology Research Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Charles E SpivakElectrophysiology Research Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Carl R LupicaElectrophysiology Research Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Suzanne M UnderhillLaboratory of Molecular and Cellular Neurobiology, Intramural Research Program, National Institute of Mental Health, Bethesda, MD 20892, USA.
Susan G AmaraLaboratory of Molecular and Cellular Neurobiology, Intramural Research Program, National Institute of Mental Health, Bethesda, MD 20892, USA.
Andrii DomanskyiInstitute of Biotechnology, HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
Jenni E AnttilaInstitute of Biotechnology, HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
Mikko AiravaaraInstitute of Biotechnology, HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
Bruce T HopeNeuronal Ensembles in Drug Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
F Kent HamraDepartment of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Christopher T RichieOptogenetics and Transgenic Technology Core/Genetic Engineering and Viral Vector Core, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Brandon K HarveyMolecular Mechanisms of Cellular Stress and Inflammation Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA; Optogenetics and Transgenic Technology Core/Genetic Engineering and Viral Vector Core, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: bharvey@mail.nih.gov.
Funding
Transgenic Resources for Neuroscience ResearchZICMH002901 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI AMARA, SUSAN · 2009 to 2025
$36.5MCharacterization of neuronal ensembles activated during drug-induced behaviorZIADA000467 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HOPE, BRUCE · 2009 to 2025
$35.8MStructure, Function and Pharmacology of Neurotransmitter Reuptake SystemsZIAMH002946 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI AMARA, SUSAN · 2013 to 2025
$26.6MCellular mechanisms of neuronal dysfunction in addiction and neurodegenerationZIADA000618 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HARVEY, BRANDON · 2017 to 2025
$12.9MGene Delivery and AddictionZIADA000526 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HARVEY, BRANDON · 2009 to 2022
$3.2MGene Therapy And NeurodegenerationZIADA000443 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HARVEY, BRANDON · 2009 to 2020
$2.7MIntramural NIH HHS ZIA DA000443Intramural NIH HHS ZIA DA000526Intramural NIH HHS ZIA DA000618
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.
Indexed as
CRISPR-Cas SystemsAdult Germline Stem CellsAnimalsBrainCRISPR-Associated Protein 9Deoxyribonuclease IDependovirusDisease Models, AnimalDopamine Plasma Membrane Transport ProteinsDopaminergic NeuronsGene EditingGene Knock-In TechniquesGene Knockout TechniquesGene TargetingGenetic VectorsIntegrasesCre recombinaseCRISPR-Associated Protein 9Deoxyribonuclease IDopamine Plasma Membrane Transport ProteinsIntegrasesLuminescent ProteinsRed Fluorescent ProteinRNA, Guide, CRISPR-Cas SystemsTyrosine 3-MonooxygenaseAAVbrainCRISPR-Cas9genome editinglsl-Cas9MANFspermatogonial stem cellstransgenic rat
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