Overview

The Cck-CreER (or Cck-CreERT2) knock-in allele both abolishes cholecystokinin (Cck) gene function and expresses the CreER^T2 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.

Donating Investigator

Z. Josh Huang, Cold Spring Harbor Laboratory

Genetic overview

Genetic Background	Generation

Cck^{tm2.1(cre/ERT2)Zjh}

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing, Inducible)	Cck	cholecystokinin

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Research Applications

Research Tools
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Cck-CreER (or Cck-CreERT2) knock-in allele both abolishes cholecystokinin (Cck) gene function and expresses the CreER^T2 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 CreER^T2 fusion gene (Cre-ER^T2; 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 (Tyr^c-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.

Expression Data

Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Following tamoxifen administration, Cre recombinase activity is observed in cholecystokinin positive neurons in cortex (both interneurons and pyramidal neurons).

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

NIH Neuroscience Blueprint Cre Driver Network. 2009. Cre recombinase-expressing mice generated for the NIH Neuroscience Blueprint Cre Driver Network MGI Direct Data SubmissionMGI: 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):995-1013PubMed: 21943598 MGI: J:177261

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Genetics

Cck^{tm2.1(cre/ERT2)Zjh}

Allele Symbol: Cck^{tm2.1(cre/ERT2)Zjh}

Allele Name	targeted mutation 2.1, Z Josh Huang
Allele Type	Targeted (Recombinase-expressing, Inducible)
Allele Synonym(s)	Cck^{tm2.1(cre/ERT2)Zjh}; targeted mutation 2.1, Z Josh Huang
Gene Symbol and Name	Cck, cholecystokinin
Gene Synonym(s)
Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Following tamoxifen administration, Cre recombinase activity is observed in cholecystokinin positive neurons in cortex (both interneurons and pyramidal neurons).
Strain of Origin	C57BL/6
Chromosome	9
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 initiation codon 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 then bred together for many more generations (and the FLPe transgene was removed).
Mutations Made By	Z. Josh Huang, Cold Spring Harbor Laboratory

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Research Tools
- Genetics Research
  - Tissue/Cell Markers: neurons
  - Tissue/Cell Markers: Cre-lox System
  - Mutagenesis and Transgenesis
  - Tissue/Cell Markers
  - Mutagenesis and Transgenesis: Cre-lox System
- Neurobiology Research
  - cell marker
- Cre-lox System
  - Cre Recombinase Expression
  - Cre Recombinase Expression: Inducible
Neurobiology Research
- Cre-lox System
  - Cre Recombinase expression in neural tissue

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Cck^{tm2.1(cre/ERT2)Zjh}/Cck⁺
involves: C57BL/6 * SJL

mammalian phenotype

no phenotypic analysis

References

NIH Neuroscience Blueprint Cre Driver Network. 2009. Cre recombinase-expressing mice generated for the NIH Neuroscience Blueprint Cre Driver Network MGI Direct Data SubmissionMGI: 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):995-1013PubMed: 21943598 MGI: J:177261

Additional - Cck^{tm2.1(cre/ERT2)Zjh} related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Cck^{tm2.1(cre/ERT2)Zjh}
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Cck^{tm2.1(cre/ERT2)Zjh}/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012710 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Cck<tm2.1(cre/ERT2)Zjh>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Ccktm2.1(cre/ERT2)Zjh

Allele Symbol: Ccktm2.1(cre/ERT2)Zjh

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Ccktm2.1(cre/ERT2)Zjh/Cck+involves: C57BL/6 * SJL

mammalian phenotype

References

Additional - Ccktm2.1(cre/ERT2)Zjh related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Cck^{tm2.1(cre/ERT2)Zjh}

Allele Symbol: Cck^{tm2.1(cre/ERT2)Zjh}

Genotype: Cck^{tm2.1(cre/ERT2)Zjh}/Cck⁺
involves: C57BL/6 * SJL

Additional - Cck^{tm2.1(cre/ERT2)Zjh} related