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

• DOI: 10.1016/j.celrep.2021.109123
• Publication Date: 2021-05-11T15:57:44Z
• Authors: 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
• Keywords: Cre recombinase

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