Generation of a DAT-P2A-Flpo mouse line for intersectional genetic targeting of dopamine neuron subpopulations

Daniel J Kramer; Erin E Aisenberg; Polina Kosillo; Drew Friedmann; David A Stafford; Angus Yiu-Fai Lee; Liqun Luo; Dirk Hockemeyer; John Ngai; Helen S Bateup

doi:10.1016/j.celrep.2021.109123

Generation of a DAT-P2A-Flpo mouse line for intersectional genetic targeting of dopamine neuron subpopulations

Cell Rep. 2021 May 11;35(6):109123. doi: 10.1016/j.celrep.2021.109123.

Authors

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
² Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
³ Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
⁴ Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
⁵ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Innovative Genomics Institute, University of California, Berkeley, CA 94720, USA.
⁶ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
⁷ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: bateup@berkeley.edu.

Abstract

Dopaminergic projections exert widespread influence over multiple brain regions and modulate various behaviors including movement, reward learning, and motivation. It is increasingly appreciated that dopamine neurons are heterogeneous in their gene expression, circuitry, physiology, and function. Current approaches to target dopamine neurons are largely based on single gene drivers, which either label all dopamine neurons or mark a subset but concurrently label non-dopaminergic neurons. Here, we establish a mouse line with Flpo recombinase expressed from the endogenous Slc6a3 (dopamine active transporter [DAT]) locus. DAT-P2A-Flpo mice can be used together with Cre-expressing mouse lines to efficiently and selectively label dopaminergic subpopulations using Cre/Flp-dependent intersectional strategies. We demonstrate the utility of this approach by generating DAT-P2A-Flpo;NEX-Cre mice that specifically label Neurod6-expressing dopamine neurons, which project to the nucleus accumbens medial shell. DAT-P2A-Flpo mice add to a growing toolbox of genetic resources that will help parse the diverse functions mediated by dopaminergic circuits.

Keywords: DAT; DAT-dopamine neurons; Flp recombinase; Neurod6; TrailMap; intersectional genetics; nucleus accumbens; substantia nigra pars compacta; ventral tegmental area.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Dopamine Plasma Membrane Transport Proteins / metabolism*
Dopaminergic Neurons / metabolism*
Humans
Mice

Substances

Dopamine Plasma Membrane Transport Proteins
Slc6a3 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding