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tTARGIT AAVs mediate the sensitive and flexible manipulation of intersectional neuronal populations in mice.

Citation
Sabatini, P., et al. “Ttargit Aavs Mediate The Sensitive And Flexible Manipulation Of Intersectional Neuronal Populations In Mice.”. Elife.
Center University of Michigan
Author Paul Sabatini V, Jine Wang, Alan C Rupp, Alison H Affinati, Jonathan N Flak, Chien Li, David P Olson, Martin G Myers
Keywords energy expenditure, intersectional populations, Leptin receptor, medicine, mouse, neuroscience, tetracycline transactivator, ventromedial hypothalamus
Abstract

While Cre-dependent viral systems permit the manipulation of many neuron types, some cell populations cannot be targeted by a single DNA recombinase. Although the combined use of Flp and Cre recombinases can overcome this limitation, insufficient recombinase activity can reduce the efficacy of existing Cre+Flp-dependent viral systems. We developed a sensitive dual recombinase-activated viral approach: tTA-driven Recombinase-Guided Intersectional Targeting (tTARGIT) adeno-associated viruses (AAVs). tTARGIT AAVs utilize a Flp-dependent tetracycline transactivator (tTA) 'Driver' AAV and a tetracycline response element-driven, Cre-dependent 'Payload' AAV to express the transgene of interest. We employed this system in mice to manipulate LepRb neurons of the ventromedial hypothalamus (VMH; LepRb neurons) while omitting neighboring LepRb populations. We defined the circuitry of LepRb neurons and roles for these cells in the control of food intake and energy expenditure. Thus, the tTARGIT system mediates robust recombinase-sensitive transgene expression, permitting the precise manipulation of previously intractable neural populations.

Year of Publication
2021
Journal
eLife
Volume
10
Date Published
03/2021
ISSN Number
2050-084X
DOI
10.7554/eLife.66835
Alternate Journal
Elife
PMID
33704065
PMCID
PMC8026215
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