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Recombinase-Dependent Mouse Lines for Chemogenetic Activation of Genetically Defined Cell Types.


ABSTRACT: Chemogenetic technologies, including the mutated human Gq-coupled M3 muscarinic receptor (hM3Dq), have greatly facilitated our ability to directly link changes in cellular activity to altered physiology and behavior. Here, we extend the hM3Dq toolkit with recombinase-responsive mouse lines that permit hM3Dq expression in virtually any cell type. These alleles encode a fusion protein designed to increase effective expression levels by concentrating hM3Dq to the cell body and dendrites. To illustrate their broad utility, we targeted three different genetically defined cell populations: noradrenergic neurons of the compact, bilateral locus coeruleus and two dispersed populations, Camk2a+ neurons and GFAP+ glia. In all three populations, we observed reproducible expression and confirmed that activation of hM3Dq is sufficient to dose-dependently evoke phenotypic changes, without extreme phenotypes associated with hM3Dq overexpression. These alleles offer the ability to non-invasively control activity of diverse cell types to uncover their function and dysfunction at any developmental stage.

SUBMITTER: Sciolino NR 

PROVIDER: S-EPMC4915594 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Recombinase-Dependent Mouse Lines for Chemogenetic Activation of Genetically Defined Cell Types.

Sciolino Natale R NR   Plummer Nicholas W NW   Chen Yu-Wei YW   Alexander Georgia M GM   Robertson Sabrina D SD   Dudek Serena M SM   McElligott Zoe A ZA   Jensen Patricia P  

Cell reports 20160602 11


Chemogenetic technologies, including the mutated human Gq-coupled M3 muscarinic receptor (hM3Dq), have greatly facilitated our ability to directly link changes in cellular activity to altered physiology and behavior. Here, we extend the hM3Dq toolkit with recombinase-responsive mouse lines that permit hM3Dq expression in virtually any cell type. These alleles encode a fusion protein designed to increase effective expression levels by concentrating hM3Dq to the cell body and dendrites. To illustr  ...[more]

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