Overview

Also Known As:Penk-2A-CreERT2-D

These knockin mice express a tamoxifen-inducible cre recombinase from the endogenous promoter/enhancer elements of the preproenkephalin locus. When induced, cre activity is observed in the striatum, olfactory tubercle, and sparse cells in the dentate gyrus and cortex.

Donating Investigator

Hongkui Zeng, Allen Institute for Brain Science

Genetic overview

Genetic Background	Generation

Penk^{tm1.1(cre/ERT2)Hze}

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing, Inducible)	Penk	preproenkephalin

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Research Applications

Research Tools
Neurobiology Research
Cancer Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice heterozygous for the Penk-2A-CreERT2-D targeted mutation (also called Penk-2A-CreERT2-Δ or Penk-2A-CreERT2-Δneo) are viable and fertile. The Penk-2A-CreERT2-D targeted mutation has an in-frame F2A peptide cleavage signal and a CreER^T2 fusion gene (CreERT2 fusion protein) inserted downstream of the preproenkephalin translational STOP codon.

As such, Penk-2A-CreERT2-D mice have both endogenous gene and CreERT2 fusion protein expression directed to Penk-expressing cells by the endogenous promoter/enhancer elements of the preproenkephalin locus. CreERT2 fusion gene activity is inducible; observed following tamoxifen administration. When Penk-2A-CreERT2-D mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of floxed sequences in the Penk-expressing cells of the double mutant offspring.

Specifically, the donating investigator reports that Cre recombinase expression (in situ hybridization) is strong in striatum, in olfactory tubercle, and in sparse dentate gyrus and cortex. Furthermore, Cre recombinase expression (in situ hybridization) is observed weakly throughout the brain. Tamoxifen-inducible Cre recombinase activity recapitulates the endogenous Penk expression pattern, but with a relatively low efficiency of induction. The donating investigator reports no Cre recombinase expression (no reporter gene expression) is observed prior to tamoxifen exposure. The donating investigator did not examine CreERT2 activity in tissues other than brain, and did not attempt to generate homozygous mice to date (July 2013).

For characterization information, see images at the Allen Institute for Brain Science website (Penk-2A-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

The Penk-2A-CreERT2-D targeted mutation (also called Penk-2A-CreERT2-Δ or Penk-2A-CreERT2-Δneo) has a CreER^T2 fusion gene inserted downstream of the preproenkephalin translational STOP codon, with both genes separated by an in-frame F2A peptide cleavage signal (to promote expression of both individual genes). The specific details are below.

The targeting vector contained, from 5' to 3',
a partial Penk intron 1 sequence containing an frt3 site,
a partial Penk exon 2 sequence up to (but not including) the endogenous stop codon,
a foot-and-mouth disease virus self-cleaving 2A peptide sequence (FMDV 2A or F2A; to promote individual expression the genes before and after it) that is in-frame with the Penk coding sequence,
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) that is in-frame with the Penk coding sequence,
a bovine growth hormone polyA signal,
an AttB site,
a PGK-Neo-polyA cassette,
an frt5 site,
an mRNA splice acceptor,
the 3' portion of the hygromycin gene with SV40 polyA signal,
an AttP site,
and genomic sequence from the Penk locus starting 509 bp downstream of the endogenous stop codon (to create a 511 bp deletion downstream of, and including, the stop codon).

This targeting vector was electroporated into (129S6/SvEvTac x C57BL/6)F1-derived G4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were bred to PhiC31-expressing mice (C57BL/6J congenic background; see Stock No. 007743) to delete the AttB/AttP-flanked sequences (PGK-neo-polyA::frt5::mRNA splice acceptor::3'hygro::SV40 polyA) and replace it with the recombined AttB/AttP site (AttL). The resulting Penk-2A-CreERT2-D mice were bred with C57BL/6J wildtype mice for several generations (and the PhiC31 transgene was removed) prior to sending generation N7F1 males to The Jackson Laboratory Repository in 2013. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Upon arrival, males were used to cryopreserve sperm. To establish the living Penk-2A-CreERT2-D mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).

Expression Data

Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Cre recombinase expression (in situ hybridization) is strong in striatum, in olfactory tubercle, and in sparse dentate gyrus and cortex, and is observed weakly throughout the brain.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Harris JA; Hirokawa KE; Sorensen SA; Gu H; Mills M; Ng LL; Bohn P; Mortrud M; Ouellette B; Kidney J; Smith KA; Dang C; Sunkin S; Bernard A; Oh SW; Madisen L; Zeng H. 2014. Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation. Front Neural Circuits 8:76PubMed: 25071457 MGI: J:220523

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Genetics

Penk^{tm1.1(cre/ERT2)Hze}

Allele Symbol: Penk^{tm1.1(cre/ERT2)Hze}

Allele Name	targeted mutation 1.1, Hongkui Zeng
Allele Type	Targeted (Recombinase-expressing, Inducible)
Allele Synonym(s)	Penk-2A-CreERT2; Penk-2A-CreERT2-DeltaNeo
Gene Symbol and Name	Penk, preproenkephalin
Gene Synonym(s)
Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Cre recombinase expression (in situ hybridization) is strong in striatum, in olfactory tubercle, and in sparse dentate gyrus and cortex, and is observed weakly throughout the brain.
Strain of Origin	(129S6/SvEvTac x C57BL/6NCrl)F1
Chromosome	4
Molecular Note	A targeting vector contained a partial Penk intron 1 sequence containing an frt3 site, a partial Penk exon 2 sequence up to (but not including) the endogenous stop codon, a self-cleaving T2A sequence in-frame with the Nxph4 coding sequence, a cre/ERT2 fusion gene, a bovine growth hormone polyA signal, an AttB site, a PGK-Neo-polyA cassette, an frt5 site, an mRNA splice acceptor, the 3' portion of the hygromycin gene with SV40 polyA signal, an AttP site and genomic sequence from the Penk locus starting 509 bp downstream of the endogenous stop codon (to create a 511 bp deletion including, the stop codon). This targeting vector was electroporated into G4 ES cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were bred to PhiC31-expressing mice to delete the AttB/AttP-flanked sequences and replace it with the recombined AttB/AttP site (AttL).

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

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

Mammalian Phenotype Terms by Genotype

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

Genotype: Penk^{tm1.1(cre/ERT2)Hze}/?
involves: 129S6/SvEvTac * C57BL/6NCrl

mammalian phenotype

no phenotypic analysis
- Normal - no details available; cre expression only was analyzed

References

Harris JA; Hirokawa KE; Sorensen SA; Gu H; Mills M; Ng LL; Bohn P; Mortrud M; Ouellette B; Kidney J; Smith KA; Dang C; Sunkin S; Bernard A; Oh SW; Madisen L; Zeng H. 2014. Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation. Front Neural Circuits 8:76PubMed: 25071457 MGI: J:220523

Additional - Penk^{tm1.1(cre/ERT2)Hze} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Penk
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). The phenotype of homozygous mice has not yet been determined (July 2013).
- Additional Breeding and Husbandry Support
Citation
When using the Penk-2A-CreERT2-D mouse strain in a publication, please cite the originating article(s) and include JAX stock #022862 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

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Not-For-Profit & Academic Pricing

Service/Product	Description	Price
	Heterozygous or Wildtype for Penk<tm1.1(cre/ERT2)Hze>

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Penk<tm1.1(cre/ERT2)Hze>/J	$2595.00
Frozen Mouse Embryo	B6.Cg-Penk<tm1.1(cre/ERT2)Hze>/J	$2595.00
Frozen Mouse Embryo	B6.Cg-Penk<tm1.1(cre/ERT2)Hze>/J	$3373.50
Frozen Mouse Embryo	B6.Cg-Penk<tm1.1(cre/ERT2)Hze>/J	$3373.50

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:Penk-2A-CreERT2-D

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Penktm1.1(cre/ERT2)Hze

Allele Symbol: Penktm1.1(cre/ERT2)Hze

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Penktm1.1(cre/ERT2)Hze/?involves: 129S6/SvEvTac * C57BL/6NCrl

mammalian phenotype

References

Additional - Penktm1.1(cre/ERT2)Hze 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 - Not-For-Profit & Academic 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

Penk^{tm1.1(cre/ERT2)Hze}

Allele Symbol: Penk^{tm1.1(cre/ERT2)Hze}

Genotype: Penk^{tm1.1(cre/ERT2)Hze}/?
involves: 129S6/SvEvTac * C57BL/6NCrl

Additional - Penk^{tm1.1(cre/ERT2)Hze} related