tTARGIT AAVs mediate the sensitive and flexible manipulation of intersectional neuronal populations in mice
© 2021, Sabatini et al..
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 Slc17a6FlpO;LeprCre mice to manipulate LepRb neurons of the ventromedial hypothalamus (VMH; LepRbVMH neurons) while omitting neighboring LepRb populations. We defined the circuitry of LepRbVMH 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
eLife - 10(2021) vom: 11. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sabatini, Paul V [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.12.2021 Date Revised 14.04.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.7554/eLife.66835 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322611407 |
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| 245 | 1 | 0 | |a tTARGIT AAVs mediate the sensitive and flexible manipulation of intersectional neuronal populations in mice |
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| 500 | |a Date Completed 07.12.2021 | ||
| 500 | |a Date Revised 14.04.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021, Sabatini et al. | ||
| 520 | |a 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 Slc17a6FlpO;LeprCre mice to manipulate LepRb neurons of the ventromedial hypothalamus (VMH; LepRbVMH neurons) while omitting neighboring LepRb populations. We defined the circuitry of LepRbVMH 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a energy expenditure | |
| 650 | 4 | |a intersectional populations | |
| 650 | 4 | |a leptin receptor | |
| 650 | 4 | |a medicine | |
| 650 | 4 | |a mouse | |
| 650 | 4 | |a neuroscience | |
| 650 | 4 | |a tetracycline transactivator | |
| 650 | 4 | |a ventromedial hypothalamus | |
| 700 | 1 | |a Wang, Jine |e verfasserin |4 aut | |
| 700 | 1 | |a Rupp, Alan C |e verfasserin |4 aut | |
| 700 | 1 | |a Affinati, Alison H |e verfasserin |4 aut | |
| 700 | 1 | |a Flak, Jonathan N |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chien |e verfasserin |4 aut | |
| 700 | 1 | |a Olson, David P |e verfasserin |4 aut | |
| 700 | 1 | |a Myers, Martin G |e verfasserin |4 aut | |
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