Journal article
Generation and validation of a D1 dopamine receptor Flpo knock-in mouse
Journal of neuroscience methods, Vol.415, 110345
03/2025
DOI: 10.1016/j.jneumeth.2024.110345
PMCID: PMC11878109
PMID: 39701542
Abstract
Dopamine is a powerful neuromodulator of diverse brain functions, including movement, motivation, reward, and cognition. D1-type dopamine receptors (D1DRs) are the most prevalently expressed dopamine receptors in the brain. Neurons expressing D1DRs are heterogeneous and involve several subpopulations. Although these neurons can be studied with BAC-transgenic rodents, these models have some limitations especially when considering their integration with conditional or intersectional genetic tools.
We developed a novel Drd1-P2A-Flpo (Drd1-Flpo) mouse line in which the Flpo gene was knocked in immediately after the Drd1 gene using CRISPR-Cas9. We validated the Drd1-Flpo line by confirming Flp expression and functionality specific to D1DR+ neurons with immunohistochemistry and in situ hybridization.
The Drd1-Flpo line is a useful resource for studying subpopulations of D1DR+ neurons with intersectional genetic tools.
We demonstrated brain-wide GFP expression driven by Drd1-Flpo, suggesting that this mouse line may be useful for comprehensive anatomical and functional studies in many brain regions. The Drd1-Flpo model will advance the study of dopaminergic signaling by providing a new tool for investigating the diverse roles of D1DR+ neurons and their subpopulations in brain disease.
Details
- Title: Subtitle
- Generation and validation of a D1 dopamine receptor Flpo knock-in mouse
- Creators
- Alexis M Oppman - University of IowaWilliam J Paradee - University of IowaNandakumar S Narayanan - University of IowaYoung-Cho Kim - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of neuroscience methods, Vol.415, 110345
- DOI
- 10.1016/j.jneumeth.2024.110345
- PMID
- 39701542
- PMCID
- PMC11878109
- NLM abbreviation
- J Neurosci Methods
- ISSN
- 1872-678X
- eISSN
- 1872-678X
- Publisher
- ELSEVIER
- Grant note
- National Institutes of Health: DOD20037, R01NS120987
This work was funded by DOD20037 and R01NS120987 to Nanda-kumar Narayanan. Drd1-Flpo transgenic mice were generated at the University of Iowa Genome Editing Facility, which is directed by William Paradee, PhD, and is supported in part by grants from the National Institutes of Health and the Roy J. and Lucille A. Carver College of Medicine.
- Language
- English
- Electronic publication date
- 12/17/2024
- Date published
- 03/2025
- Academic Unit
- Neurology; Iowa Neuroscience Institute; Medicine Administration
- Record Identifier
- 9984758267102771
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