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| These SLICK-H transgenic mice have expression of a CreERT2 fusion protein and an enhanced yellow fluorescent protein (EYFP) directed by two separate copies of the modified mouse Thy1 promoter region. These SLICK-H transgenic mice allow fluorescent labeling in the majority of projection neurons populations in the central and peripheral nervous system, with inducible Cre-lox genetic manipulation in the same widespread population of labeled neurons. Of note, the broader transgene expression pattern of SLICK-H transgenic mice compared to other SLICK lines facilitates widespread inducible neuron-specific conditional genetic manipulation, but renders SLICK-H transgenic mice unsuitable for single neuron imaging purposes. | |||||||||||||||||||
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Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Hemizygote x Noncarrier (Female x Male) 08-JUN-11 Species laboratory mouse Generation F?+F1 (29-SEP-11)
Generation DefinitionsDonating Investigator Paul Young, University College Cork Description
The "single-neuron labeling inducible Cre-mediated knockout" (SLICK) transgene is designed with two separate copies of the modified mouse Thy1 promoter region (each containing the sequences required for neuronal expression but lacking the sequences required for expression in non-neural cells) driving expression of a CreERT2 fusion protein and an enhanced yellow fluorescent protein (EYFP). Mice harboring the SLICK transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. mRNA coexpression of both CreERT2 and YFP is highly correlated. YFP expression is directed primarily to projection neurons with variations in the extent and brightness of labeling observed in different founder lines (see below). CreERT2 fusion gene activity is inducible; observed at high levels following tamoxifen administration (see below). When SLICK transgenic mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Thy1-expressing cells of the double mutant offspring.SLICK transgenic mice derived from founder line H (SLICK-H) exhibit both widespread and strong expression of YFP in projection neurons throughout the peripheral and central nervous system; and are thus not suitable for single neuron imaging purposes. Transgene expression is restricted to neurons; no YFP fluorescence or tamoxifen-induced Cre recombinase activity is observed in astrocytes, oligodendrocytes, or non-neural populations. As designed, transgene expression is limited during early developmental stages due to the late onset/activity of the Thy1 promoter used in these mice. Transgene expression increases postnatally, and robust YFP expression/highly-efficient induction of recombination in most projection neuron populations is possible in adult SLICK-H mice from six weeks of age and older. Specifically, SLICK-H transgenic mice have extensive/strong YFP labeling of cell somas in the cortex (visual, parietal, somatosensory, motor, insular, piriform and entorhinal areas), the major hippocampal fields (except CA2), the amygdala (basal nucleus), the inferior colliculus, the superior colliculus, the thalamic nuclei, the brainstem nuclei, the anterior olfactory nucleus, the cerebellum (granule and Purkinje cells), and olfactory bulb (mitral cells). Outside the brain, extensive/strong YFP labeling is found in the spinal cord (sensory neurons and motor neurons), the dorsal root ganglion neurons, and the retina (photoreceptors and retinal ganglion cells). YFP expression can be detected by direct YFP fluorescence as well as immunohistochemical methods. In addition, SLICK-H transgenic mice have high tamoxifen-induced Cre recombinase efficiency/activity in projection neurons of the cortex, hippocampus, amygdala, brainstem, thalamus, inferior colliculus, superior colliculus, spinal cord, dorsal root ganglia, and retina following tamoxifen administration. CreERT2 activation in the absence of tamoxifen is minimal (less than 1% of the levels observed after tamoxifen induction). Therefore, these SLICK-H transgenic mice allow fluorescent labeling in the majority of projection neurons populations in the central and peripheral nervous system, with inducible Cre-lox genetic manipulation in the same widespread population of labeled neurons.
Other SLICK transgenic lines have sparse labeling of single neurons. The SLICK-A mice (Stock No. 007606) express the transgene in small subsets of motor neurons, dorsal root ganglion neurons, some hippocampal regions and cortical layer V; but fluorescence is less uniform with leaky and less-efficient Cre recombinase activity. The SLICK-V mice (Stock No. 007610) express the transgene sparsely in neurons of the central nervous system. Therefore, the broader transgene expression pattern of SLICK-H transgenic mice facilitates widespread inducible neuron-specific conditional genetic manipulation, but renders SLICK-H transgenic mice unsuitable for single neuron imaging purposes.
The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.
This strain is one of many from the same transgene creator/donating investigator with fluorescent protein expression/neurobiological research applications, including:
SLICK line A (Stock No. 007606), SLICK line V (Stock No. 007610), SLICK line H (Stock No. 012708), GAD67-GFP line 3 (Stock No. 007673), Thy1-GFP line O (Stock No. 007919), Thy1-YFP line G (line 17) (Stock No. 014130), Thy1-CFP line I (Stock No. 014131), Thy1-ChR2-YFP line 18 (Stock No. 007612), Thy1-ChR2-YFP line 9 (Stock No. 007615), Thy1-eNpHR-YFP line 2 (Stock No. 012332), Thy1-eNpHR-YFP line 4 (Stock No. 012334), Thy1-vChR1-YFP line 1 (Stock No. 012341), Thy1-vChR1-YFP line 4 (Stock No. 012344), Thy1-vChR1-YFP line 8 (Stock No. 012348), Thy1-mhChR2-YFP line 20 (Stock No. 012350), Prv-mhChR2-YFP line 15 (Stock No. 012355), ChAT-ChR2-YFP line 5 (Stock No. 014545), ChAT-ChR2-YFP line 6 (Stock No. 014546), VGAT-ChR2-YFP line 8 (Stock No. 014548), TpH2-ChR2-YFP line 5 (Stock No. 014555), and R26-CAG-LSL-2XChETA-tdTomato reporter mice (Stock No. 017455).Development
The "single-neuron labeling with inducible Cre-mediated knockout" (SLICK) transgene was designed with a CreERT2 fusion gene, two copies of the mouse Thy1 promoter, and an enhanced yellow fluorescent protein (EYFP) cDNA sequence. The CreERT2 fusion gene (Cre-ERT2) is Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain. Each Thy1 promoter region is a modified regulatory region of the "murine thy1.2 gene" (extending from the promoter to the intron following exon 4, excluding exon 3 and its flanking introns). The two copies are placed "back to back" to function bidirectionally; one copy drives expression of CreERT2, the other copy drives expression of EYFP. The SLICK transgene was microinjected into (C57BL6/J x CBA)F1 fertilized embryos. Transgenic founders were bred to C57BL6/J mice for analysis of expression patterns. Founder line H (SLICK-H) was subsequently established and backcrossed to C57BL/6J for an additional four generations. At some point, transgenic mice were also bred to CD1 mice and/or Gt(ROSA)26Sor mutant mice (on a C57B/6 genetic background; see Stock No. 003474). SLICK-H mice were maintained on a mixed CD1;C57BL/6J genetic background (and the Gt(ROSA)26Sor mutation was removed) prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (357 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Introduction to Cre-lox technology
Phenotype
Phenotype Information
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Estrogen Receptor 1; ESR1 (ESR1)
Migraine with or without Aura, Susceptibility to, 1 (ESR1)
Myocardial Infarction, Susceptibility to (ESR1)
This mouse can be used to support research in many areas including:
YFP relatedNeurobiology Research
Cre-lox System
Cre Recombinase expression in neural tissue
Fluorescent protein expression in neural tissue
Research Tools
Cre-lox System
Cre Recombinase Expression
Cre Recombinase Expression: Inducible
Developmental Biology Research
transplantation marker for embryonic and adult tissue
Fluorescent Proteins
Genetics Research
Mutagenesis and Transgenesis: Cre-lox System
Tissue/Cell Markers: Cre-lox System
Tissue/Cell Markers: neurons
Tissue/Cell Markers: transplantation marker for embryonic and adult tissue
Neurobiology Research
cell marker
cre relatedResearch Tools
Fluorescent Proteins
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Cre-lox System
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Thy1-cre/ERT2,-EYFP)HGfng | ||
|---|---|---|---|
| Allele Name | transgene insertion H, Guoping Feng | ||
| Allele Type | Transgenic (Cre/Flp) | ||
| Common Name(s) | SLICK-H; | ||
| Mutation Made By | Guoping Feng, Massachusetts Institute of Technology | ||
| Strain of Origin | (C57BL/6J x CBA)F1 | ||
| Site of Expression | YFP is expressed in projection neuron populations. | ||
| Expressed Gene | ESR1, estrogen receptor 1, human | ||
| Expressed Gene | YFP, Yellow Fluorescent Protein, jellyfish | ||
| Yellow Fluorescent Protein (YFP) is a derivative of Green Fluorescent Protein (GFP), a versatile reporter molecule which has found use in many biological applications. The original molecule has been modified in order to enhance fluorescence intensity and shift the wavelength emitted when excited. When YFP is utilized in a transgenic construct, tissue expressing sufficient amounts of YFP will fluoresce yellowish-green when exposed to a 513 nm light source. | |||
| Expressed Gene | cre, cre recombinase, bacteriophage P1 | ||
| Cre recombinase is an enzyme derived from the bacteriophage P1 that specifically recognizes loxP sites. Cre has been shown to effectively mediate the excision of DNA located between loxP sites. After the excision event, the DNA ends recombine leaving a single loxP site in place of the intervening sequence. | |||
| Promoter | Thy1, thymus cell antigen 1, theta, mouse, laboratory | ||
| Driver Note | Thy1 | ||
| Inducible Note | induced by tamoxifen | ||
| Molecular Note | The transgene was designed with a creERT2 fusion gene, two copies of the mouse Thy1 promoter, and an enhanced yellow fluorescent protein (EYFP) cDNA sequence. The creERT2 fusion gene (cre/ERT2) is cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain. Each Thy1 promoter region is a modified regulatory region of the murine thy1.2 gene (extending from the promoter to the intron following exon 4, excluding exon 3 and its flanking introns). The twocopies are placed "back to back" to function bidirectionally; one copy drives expression of CreERT2, the other copy drives expression of EYFP. Founder line H (SLICK-H) was subsequently established and backcrossed to C57BL/6J for 4 generations. [MGI Ref ID J:134019] | ||
| Gene Symbol and Name | Tg(Thy1-cre/ERT2,-EYFP)HGfng, transgene insertion H, Guoping Feng | ||
| Chromosome | UN | ||
| Gene Common Name(s) | SLICK-H; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Thy1-cre/ERT2,-EYFP), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Caroni P. 1997. Overexpression of growth-associated proteins in the neurons of adult transgenic mice. J Neurosci Methods 71(1):3-9. [PubMed: 9125370] [MGI Ref ID J:123610]
Feil R; Wagner J; Metzger D; Chambon P. 1997. Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. Biochem Biophys Res Commun 237(3):752-7. [PubMed: 9299439] [MGI Ref ID J:79835]
Young P; Qiu L; Wang D; Zhao S; Gross J; Feng G. 2008. Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice. Nat Neurosci :. [PubMed: 18454144] [MGI Ref ID J:134019]
Additional References
Tg(Thy1-cre/ERT2,-EYFP)HGfng relatedDeisseroth K; Feng G; Majewska AK; Miesenbock G; Ting A; Schnitzer MJ. 2006. Next-generation optical technologies for illuminating genetically targeted brain circuits. J Neurosci 26(41):10380-6. [PubMed: 17035522] [MGI Ref ID J:122791]
Heimer-McGinn V; Young P. 2011. Efficient inducible Pan-neuronal cre-mediated recombination in SLICK-H transgenic mice. Genesis 49(12):942-9. [PubMed: 21671347] [MGI Ref ID J:180876]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype siblings or to C57BL/6J inbred mice (Stock No. 000664). The donating investigator has not tried to maintain a homozygous colony. Mating System Hemizygote x Noncarrier (Female x Male) 08-JUN-11 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(Thy1-cre/ERT2,-EYFP)HGfng
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(Thy1-cre/ERT2,-EYFP)HGfng x Noncarrier $296.00 Noncarrier x Hemizygous for Tg(Thy1-cre/ERT2,-EYFP)HGfng Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(Thy1-cre/ERT2,-EYFP)HGfng
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(Thy1-cre/ERT2,-EYFP)HGfng x Noncarrier $384.80 Noncarrier x Hemizygous for Tg(Thy1-cre/ERT2,-EYFP)HGfng Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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