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PMID: 20023653 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A robust and high-throughput Cre reporting and characterization system for the whole mouse brain.

Nature neuroscience ·Vol. 13 ·No. 1 ·2010-01-00 ·Pages 133-40

Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, Ng LL, Palmiter RD, Hawrylycz MJ, Jones AR, Lein ES, Zeng H

Abstract

The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universally responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in several Cre-driver lines, including new Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation.

MeSH Terms
Animals Bacterial Proteins/genetics Brain/cytology,metabolism Dendrites/metabolism Gene Transfer Techniques Integrases/genetics,physiology Luminescent Proteins/genetics Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Confocal Neurons/cytology Promoter Regions, Genetic Recombination, Genetic Regulatory Sequences, Nucleic Acid Tamoxifen/pharmacology Tissue Distribution Viral Proteins/genetics,metabolism
Chemicals
Bacterial Proteins Luminescent Proteins Viral Proteins yellow fluorescent protein, Bacteria Tamoxifen Cre recombinase Integrases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Madisen Linda
Allen Institute for Brain Science, Seattle, Washington, USA.
Zwingman Theresa A
Sunkin Susan M
Oh Seung Wook
Zariwala Hatim A
Gu Hong
Ng Lydia L
Palmiter Richard D
Hawrylycz Michael J
Jones Allan R
Lein Ed S
Zeng Hongkui
References (44)
44 references, click to expand
  1. Targeted gene expression in dopamine and serotonin neurons of the mouse brain.
    J Neurosci Methods. 2005 Apr 15;143(1):27-32 PMID: 15763133
  2. High-efficiency FLP and PhiC31 site-specific recombination in mammalian cells.
    PLoS One. 2007 Jan 17;2(1):e162 PMID: 17225864
  3. Genome-wide atlas of gene expression in the adult mouse brain.
    Nature. 2007 Jan 11;445(7124):168-76 PMID: 17151600
  4. Genetically-directed, cell type-specific sparse labeling for the analysis of neuronal morphology.
    PLoS One. 2008;3(12):e4099 PMID: 19116659
  5. High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression.
    PLoS One. 2008 Apr 16;3(4):e2005 PMID: 18414675
  6. Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning.
    Neuron. 2006 Feb 16;49(4):603-15 PMID: 16476668
  7. A global double-fluorescent Cre reporter mouse.
    Genesis. 2007 Sep;45(9):593-605 PMID: 17868096
  8. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus.
    BMC Dev Biol. 2001;1:4 PMID: 11299042
  9. A new logic for DNA engineering using recombination in Escherichia coli.
    Nat Genet. 1998 Oct;20(2):123-8 PMID: 9771703
  10. Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage.
    J Neurosci. 2002 Aug 1;22(15):6309-14 PMID: 12151506
  11. Advances in fluorescent protein technology.
    J Cell Sci. 2007 Dec 15;120(Pt 24):4247-60 PMID: 18057027
  12. Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector.
    Nat Biotechnol. 2004 May;22(5):589-94 PMID: 15064769
  13. Visualizing circuits and systems using transgenic reporters of neural activity.
    Curr Opin Neurobiol. 2007 Oct;17(5):567-71 PMID: 18036810
  14. Retina- and ventral forebrain-specific Cre recombinase activity in transgenic mice.
    Genesis. 2000 Feb;26(2):130-2 PMID: 10686607
  15. Deletion of GAD67 in dopamine receptor-1 expressing cells causes specific motor deficits.
    Genesis. 2008 Jul;46(7):357-67 PMID: 18615733
  16. hGFAP-cre transgenic mice for manipulation of glial and neuronal function in vivo.
    Genesis. 2001 Oct;31(2):85-94 PMID: 11668683
  17. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system.
    Nature. 2007 Nov 1;450(7166):56-62 PMID: 17972876
  18. Molecular taxonomy of major neuronal classes in the adult mouse forebrain.
    Nat Neurosci. 2006 Jan;9(1):99-107 PMID: 16369481
  19. Rapid and reversible chemical inactivation of synaptic transmission in genetically targeted neurons.
    Neuron. 2005 Dec 8;48(5):727-35 PMID: 16337911
  20. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates.
    Science. 2005 Oct 28;310(5748):683-5 PMID: 16254186
  21. Millisecond-timescale, genetically targeted optical control of neural activity.
    Nat Neurosci. 2005 Sep;8(9):1263-8 PMID: 16116447
  22. Postnatal development of the dopamine transporter: a quantitative autoradiographic study.
    Brain Res Dev Brain Res. 1996 Apr 30;92(2):172-81 PMID: 8738124
  23. A FLEX switch targets Channelrhodopsin-2 to multiple cell types for imaging and long-range circuit mapping.
    J Neurosci. 2008 Jul 9;28(28):7025-30 PMID: 18614669
  24. Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network.
    Science. 2007 Jul 6;317(5834):94-9 PMID: 17556551
  25. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis.
    Neuron. 2004 Jun 24;42(6):983-91 PMID: 15207242
  26. Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning.
    Science. 2008 Feb 29;319(5867):1260-4 PMID: 18218862
  27. Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors.
    J Virol. 1999 Apr;73(4):2886-92 PMID: 10074136
  28. Developmental and adult phenotyping directly from mutant embryonic stem cells.
    Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4455-60 PMID: 17360545
  29. Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain.
    BMC Bioinformatics. 2008 Mar 18;9:153 PMID: 18366675
  30. Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision.
    Genesis. 2000 Nov-Dec;28(3-4):147-55 PMID: 11105057
  31. In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2.
    Neuron. 2007 Apr 19;54(2):205-18 PMID: 17442243
  32. Mouse cortical inhibitory neuron type that coexpresses somatostatin and calretinin.
    J Comp Neurol. 2006 Nov 1;499(1):144-60 PMID: 16958092
  33. Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo.
    Nat Protoc. 2006;1(1):380-6 PMID: 17406260
  34. Generalized lacZ expression with the ROSA26 Cre reporter strain.
    Nat Genet. 1999 Jan;21(1):70-1 PMID: 9916792
  35. Neuroinformatics for genome-wide 3D gene expression mapping in the mouse brain.
    IEEE/ACM Trans Comput Biol Bioinform. 2007 Jul-Sep;4(3):382-393 PMID: 17666758
  36. Mosaic analysis with double markers in mice.
    Cell. 2005 May 6;121(3):479-92 PMID: 15882628
  37. Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs.
    J Neurosci. 2007 Sep 12;27(37):9817-23 PMID: 17855595
  38. Subregion- and cell type-restricted gene knockout in mouse brain.
    Cell. 1996 Dec 27;87(7):1317-26 PMID: 8980237
  39. Experience-dependent and cell-type-specific spine growth in the neocortex.
    Nature. 2006 Jun 22;441(7096):979-83 PMID: 16791195
  40. Genomic anatomy of the hippocampus.
    Neuron. 2008 Dec 26;60(6):1010-21 PMID: 19109908
  41. Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum.
    Dev Biol. 2004 Jun 15;270(2):393-410 PMID: 15183722
  42. A developmental switch in the response of DRG neurons to ETS transcription factor signaling.
    PLoS Biol. 2005 May;3(5):e159 PMID: 15836427
  43. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP.
    Neuron. 2000 Oct;28(1):41-51 PMID: 11086982
  44. Genetic dissection of neural circuits.
    Neuron. 2008 Mar 13;57(5):634-60 PMID: 18341986
Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
Published
2010-01-00
Epub
2009-00-20
Pages
133-40
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC2840225
Subset
IM
Grants
NIMH NIH HHS · R01 MH085500 · United States
NIMH NIH HHS · R01 MH085500-01 · United States
NIMH NIH HHS · MH085500 · United States
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