Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance.
An increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Linda
L
Madisen
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Aleena R
AR
Garner
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Daisuke
D
Shimaoka
MIT Media Lab and McGovern Institute, Massachusetts Institute of Technology, 20 Ames Street, Cambridge, MA 02139, USA.
Amy S
AS
Chuong
MIT Media Lab and McGovern Institute, Massachusetts Institute of Technology, 20 Ames Street, Cambridge, MA 02139, USA.
Nathan C
NC
Klapoetke
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Lu
L
Li
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Alexander
A
van der Bourg
Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
Yusuke
Y
Niino
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Ladan
L
Egolf
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Claudio
C
Monetti
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Hong
H
Gu
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Maya
M
Mills
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Adrian
A
Cheng
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Bosiljka
B
Tasic
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Thuc Nghi
TN
Nguyen
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
Susan M
SM
Sunkin
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK; Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
Andrea
A
Benucci
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Andras
A
Nagy
Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
Atsushi
A
Miyawaki
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Fritjof
F
Helmchen
Department of Physiology, Brain Health Research Centre, University of Otago, PO Box 913, Dunedin 9054, New Zealand.
Ruth M
RM
Empson
The Division of Brain Sciences, Department of Medicine, Imperial College London, 160 DuCane Road, London, W12 0NN, UK.
Thomas
T
Knöpfel
MIT Media Lab and McGovern Institute, Massachusetts Institute of Technology, 20 Ames Street, Cambridge, MA 02139, USA.
Edward S
ES
Boyden
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA.
R Clay
RC
Reid
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Matteo
M
Carandini
Allen Institute for Brain Science, 551 N 34(th) Street, Seattle, WA 98103, USA. Electronic address: hongkuiz@alleninstitute.org.
Hongkui
H
Zeng
D000818:Animals; D018390:Gene Targeting / Q000379:methods*; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology; D019426:Integrases / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D062308:Optogenetics / Q000379:methods*; D009924:Organ Culture Techniques; D014793:Visual Cortex / Q000737:chemistry / Q000502:physiology
C045073:Cre recombinase; D019426:Integrases