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| The Cck-CreER (or Cck-CreERT2) knock-in allele both abolishes cholecystokinin (Cck) gene function and expresses the CreERT2 fusion protein in cholecystokinin positive cortical neurons (both interneurons and pyramidal neurons) as directed by the endogenous Cck promoter/enhancer elements. Cre-ERT2 fusion gene activity is inducible by the administration of tamoxifen. | |||||||||||||||||||
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- Disease & phenotype
- Genes & alleles
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Description
Strain Information
Former Names B6(Cg)-Ccktm2.1(cre/ERT2)Zjh/J (Changed: 18-MAR-13 ) Type Mutant Stock; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Wild-type x Heterozygote (Female x Male) 21-OCT-11 Mating System Heterozygote x Wild-type (Female x Male) 21-OCT-11 Species laboratory mouse Generation N6+ (03-OCT-11)
Generation DefinitionsDonating Investigator Z. Josh Huang, Cold Spring Harbor Laboratory Description
The Cck-CreER (or Cck-CreERT2) knock-in allele both abolishes cholecystokinin (Cck) gene function and expresses the CreERT2 fusion protein from the Cck promoter/enhancer elements. The donating investigator reports that homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygotes may be expected to have a phenotype similar to other null mutations of this gene and may exhibit metabolic abnormalities of the endocrine/exocrine glands (increased pancreatic amylase).Cre-ERT2 fusion gene activity is inducible; observed following tamoxifen administration. As such, when Cck-CreERT2 mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Cck-expressing cells of the offspring. These Cck-CreERT2 mice may be useful in studying brain anatomy, physiology and behavior.
The donating investigator reports tamoxifen-inducible Cre recombinase activity recapitulates the endogenous Cck expression pattern, with moderate efficiency of induction. They report tamoxifen-inducible Cre recombinase activity is not observed prior to tamoxifen treatment. Following tamoxifen administration, Cre recombinase activity is observed in cholecystokinin positive neurons in cortex (both interneurons and pyramidal neurons). The donating investigators did not examine cre expression in subcortical neurons or in any tissues other than brain.
For characterization information, see images at the Allen Institute for Brain Science website (Cck-CreERT2 images).
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.
Development
A targeting vector was designed to insert a CreERT2 fusion gene (Cre-ERT2; Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain), an SV40 polyA signal, and an frt-flanked neo cassette into the initiation codon of the cholecystokinin locus (Cck). This construct was electroporated into C57BL/6-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric males were bred with albino C57BL/6 females (Tyrc-2J ; see Stock No. 000058), and black pups harboring the cre targeted mutation were selected. Mutant mice were then bred with Actin-FLPe mice (on a C57BL/6 congenic background (N10); see Stock No. 005703) to remove the neo selection cassette. The donating investigator reported that Cck-CreER (or Cck-CreERT2) mice were subsequently bred to C57BL/6 inbred mice for two additional generations and then bred together for many more generations (and the FLPe transgene was removed) prior to arrival at The Jackson Laboratory Repository (see SNP note below). Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the Cck-CreER colony. These Cck-CreER mice may still be segregating at the Tyr locus.A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, was performed on the first generation rederived living colony at The Jackson Laboratory Repository. This revealed 10 of 27 markers (one each on chromosomes 1, 6, 8, 9, 11, 12, 15, and 19, and two markers on chromosome 17) that were not fixed for C57BL/6 allele-type (e.g.: still segregating for allele-type markers of other genetic backgrounds). These data suggest the mice were not backcrossed to C57BL/6 prior to arrival at The Jackson Laboratory, and the colony is a mix of one or more different genetic backgrounds other than C57BL/6.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Related Strains
NIH Neuroscience Blueprint cre strains from CSHL
010774 B6(Cg)-Calb2tm1(cre)Zjh/J 013730 B6(Cg)-Calb2tm2.1(cre/ERT2)Zjh/J 012704 B6(Cg)-Crhtm1(cre)Zjh/J 010705 B6(Cg)-Dlx5tm1(cre/ERT2)Zjh/J 013048 B6(Cg)-Etv1tm1.1(cre/ERT2)Zjh/J 010776 B6(Cg)-Lhx6tm1(cre/ERT2)Zjh/J 010777 B6(Cg)-Pvalbtm1(cre/ERT2)Zjh/J 010708 B6(Cg)-Ssttm1(cre/ERT2)Zjh/J 014541 B6;129S-Nos1tm1.1(cre/ERT2)Zjh/J 014551 B6;129S4-Dlx1tm1(cre/ERT2)Zjh/J 012706 STOCK Ccktm1.1(cre)Zjh/J 010910 STOCK Corttm1(cre)Zjh/J 010702 STOCK Gad2tm1(cre/ERT2)Zjh/J 010802 STOCK Gad2tm2(cre)Zjh/J 014552 STOCK Nkx2-1tm1.1(cre/ERT2)Zjh/J 013044 STOCK Ssttm2.1(cre)Zjh/J 010908 STOCK Viptm1(cre)Zjh/J View NIH Neuroscience Blueprint cre strains from CSHL (17 strains)
017710 B6.129-Ccktm1Lcs/J 011086 C57BL/6-Tg(Cck-cre)CKres/J 012706 STOCK Ccktm1.1(cre)Zjh/J
Additional Web Information
Introduction to Cre-lox technology
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Ccktm2.1(cre/ERT2)Zjh/Cck+
involves: C57BL/6 * SJL
- no phenotypic analysis
- *normal* no phenotypic analysis (MGI Ref ID J:151755)
This mouse can be used to support research in many areas including:
cre relatedNeurobiology Research
Cre-lox System
Cre Recombinase expression in neural tissue
Research Tools
Cre-lox System
Cre Recombinase Expression
Cre Recombinase Expression: Inducible
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Cre-lox System
Tissue/Cell Markers
Tissue/Cell Markers: Cre-lox System
Tissue/Cell Markers: neurons
Neurobiology Research
cell marker
Research Tools
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Cre-lox System
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Ccktm2.1(cre/ERT2)Zjh | ||
|---|---|---|---|
| Allele Name | targeted mutation 2.1, Z Josh Huang | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Cck-CreER; | ||
| Mutation Made By | Z. Josh Huang, Cold Spring Harbor Laboratory | ||
| Strain of Origin | C57BL/6 | ||
| Site of Expression | Following tamoxifen administration, Cre recombinase activity is observed in cholecystokinin positive neurons in cortex (both interneurons and pyramidal neurons). | ||
| 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. | |||
| Driver Note | Cck | ||
| Inducible Note | induced by tamoxifen | ||
| Molecular Note | A targeting vector was designed to insert a CreERT2 fusion gene (Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain), an SV40 polyA signal, and an frt-flanked neo cassette into the initiationcodon of the cholecystokinin locus (Cck). This construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6 mice to originate the colony. Mutant mice were bred with Actin-FLPe mice (on a C57BL/6 congenic background (N10)) to remove the neo selection cassette. These Cck-CreER (or Cck-CreERT2) mice were subsequently bred to C57BL/6 inbred mice for two additional generations and thenbred together for many more generations (and the FLPe transgene was removed). [MGI Ref ID J:151755] | ||
| Gene Symbol and Name | Cck, cholecystokinin | ||
| Chromosome | 9 | ||
Genotyping
Genotyping Information
Genotyping Protocols
Ccktm2.1(cre/ERT2)Zjh, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
NIH Neuroscience Blueprint Cre Driver Network. 2009. Cre recombinase-expressing mice generated for the NIH Neuroscience Blueprint Cre Driver Network MGI Direct Data Submission :. [MGI Ref ID J:151755]
Taniguchi H; He M; Wu P; Kim S; Paik R; Sugino K; Kvitsani D; Fu Y; Lu J; Lin Y; Miyoshi G; Shima Y; Fishell G; Nelson SB; Huang ZJ. 2011. A resource of cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71(6):995-1013. [PubMed: 21943598] [MGI Ref ID J:177261]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J mice (Stock No. 000664). The donating investigator reports that homozygous mice are viable and fertile. Mating System Wild-type x Heterozygote (Female x Male) 21-OCT-11 Heterozygote x Wild-type (Female x Male) 21-OCT-11 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Heterozygous for Ccktm2.1(cre/ERT2)Zjh
Price per Pair (US dollars $) Pair Genotype $296.00 Heterozygous for Ccktm2.1(cre/ERT2)Zjh x Wild-type for Ccktm2.1(cre/ERT2)Zjh $296.00 Wild-type for Ccktm2.1(cre/ERT2)Zjh x Heterozygous for Ccktm2.1(cre/ERT2)Zjh 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 Heterozygous for Ccktm2.1(cre/ERT2)Zjh
Price per Pair (US dollars $) Pair Genotype $384.80 Heterozygous for Ccktm2.1(cre/ERT2)Zjh x Wild-type for Ccktm2.1(cre/ERT2)Zjh $384.80 Wild-type for Ccktm2.1(cre/ERT2)Zjh x Heterozygous for Ccktm2.1(cre/ERT2)Zjh 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 | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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