Overview

Also Known As:Arc^CreER

The Arc^CreER knock-in/knockout allele was designed to both abolish expression of the Arc immediate early gene and direct expression of the CreER^T2 fusion protein from the Arc promoter/enhancer elements. These mice are a Cre-lox tool that allows inducible Cre expression in Arc-expressing cells/tissues; including neurons activated by specific somatosensory, visual, and auditory stimuli. Immediate early genes (IEGs) are the connection between gene expression and a neuron's electrical/synaptic activity (which defines the neuron's response properties).

Donating Investigator

Liqun Luo, Stanford University

Genetic overview

Genetic Background	Generation
	?+N3F8 (2019-01-25 00:00:00)

Arc^{tm1.1(cre/ERT2)Luo}

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing, Inducible)	Arc	activity regulated cytoskeletal-associated protein

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Research Applications

Neurobiology Research
Research Tools

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female 4-week

333.51 Domestic price for breeder pair

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Details

Detailed Description

The Arc^CreER knock-in/knockout allele was designed to both abolish activity regulated cytoskeletal-associated protein (Arc) gene function and express CreER^T2 (CreERT2) fusion protein from the endogenous Arc promoter/enhancer elements. The donating investigator did not determine if endogenous gene mRNA/protein is expressed from the mutant allele. CreERT2 fusion protein activity is inducible; observed following tamoxifen administration. When Arc^CreER mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of floxed sequences in the Arc-expressing cells of the offspring.

Specifically, the donating investigator reports that following tamoxifen induction, Cre recombinase activity is observed in active populations of neurons in the brain in a pattern consistent with endogenous Arc expression. Some CreERT2 activity is observed in the brain prior to tamoxifen exposure (sub-populations of neurons in the brain, including in layer 6 neocortical cells and dentate gyrus granule cells, as well as sparser populations of other cell types). Additionally, a small number of offspring show Cre recombinase activity in the germline (both with or without tamoxifen). The donating investigator did not examine CreERT2 activity in tissues other than brain.

While other Arc null mutations are published with behavioral/neurological defects and embryonic lethality, the donating investigator reports that Arc^CreER homozygotes are viable and fertile with no behavioral/neurological defects grossly observed. More detailed behavioral/physiological characterization of homozygous mice has not been evaluated to date (April 2013).

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-SV40 polyA cassette followed by an FRT5-flanked pSV40-NeoR-pA cassette into the the translational start site of the activity regulated cytoskeletal-associated protein gene (Arc). The CreER^T2 fusion gene (Cre-ER^T2) is Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain. The targeting event displaced the introns and coding regions and replaced the endogenous 3prime UTRs (which contribute to mRNA destabilization and to Arc mRNA dendritic trafficking) with an exogenous SV40 polyadenylation signal (to promote high-level expression). All sequences 5prime to the translational start site are retained. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were bred to germline-active GFP-FlpO transgenic mice (mixed genetic background of CD1;FVB;C57BL/6) to delete the FRT5-flanked pSV40-NeoR-pA cassette. The resulting Arc^CreER (Arc^CreERT2) mice were bred with C57BL/6J wildtype mice for at least six generations (and the GFP-FlpO transgene was removed) prior to sending to The Jackson Laboratory Repository in 2013. Upon arrival, males were used to cryopreserve sperm. To establish the living Arc^CreER 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	Following tamoxifen induction, Cre recombinase activity is observed in active populations of neurons in the brain in a pattern consistent with endogenous Arc expression.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Guenthner CJ; Miyamichi K; Yang HH; Luo L. 2013. Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations Neuron 78(5):773-784PubMed: 23764283 MGI: J:196644

View All References

Genetics

Arc^{tm1.1(cre/ERT2)Luo}

Allele Symbol: Arc^{tm1.1(cre/ERT2)Luo}

Allele Name	targeted mutation 1.1, Liqun Luo
Allele Type	Targeted (Recombinase-expressing, Inducible)
Allele Synonym(s)	Arc^CreER; Arc^CreERT2; ArcCreER; Arc-CreER; ArcCreERT2; Arc-CreERT2
Gene Symbol and Name	Arc, activity regulated cytoskeletal-associated protein
Gene Synonym(s)
Expressed Gene	cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of Expression	Following tamoxifen induction, Cre recombinase activity is observed in active populations of neurons in the brain in a pattern consistent with endogenous Arc expression.
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	15
Molecular Note	A targeting vector was designed to insert a cre/ERT2-SV40 polyA cassette followed by an FRT5-flanked pSV40-NeoR-pA cassette into the the translational start site of the activity regulated cytoskeletal-associated protein gene (Arc). The targeting event displaced the introns and coding regions and replaced the endogenous 3' UTRs (which contribute to mRNA destabilization and to Arc mRNA dendritic trafficking) with an exogenous SV40 polyadenylation signal (to promote high-level expression). All sequences 5' to the translational start site are retained. The resulting chimeric animals were bred to germline-active GFP-FlpO transgenic mice to delete the FRT5-flanked pSV40-NeoR-pA cassette.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

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

Mammalian Phenotype Terms by Genotype

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

Genotype: Arc^{tm1.1(cre/ERT2)Luo}/Arc^{tm1.1(cre/ERT2)Luo}
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mammalian phenotype

no phenotypic analysis
- Normal - mice are viable and fertile with no overt behavioral or morphological abnormalities observed; detailed analysis of homozygotes has not been performed

References

Guenthner CJ; Miyamichi K; Yang HH; Luo L. 2013. Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations Neuron 78(5):773-784PubMed: 23764283 MGI: J:196644

Additional References

Tanaka DH; Li S; Mukae S; Tanabe T. 2019. Genetic Access to Gustatory Disgust-Associated Neurons in the Interstitial Nucleus of the Posterior Limb of the Anterior Commissure in Male Mice. Neuroscience 413:45-63PubMed: 31229633 MGI: J:282911

Additional - Arc^{tm1.1(cre/ERT2)Luo} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Generic Cre Probe
- Standard PCR:Arc
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
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).

While other Arc null mutations are published with behavioral/neurological defects and embryonic lethality, the donating investigator reports that Arc^CreER homozygotes are viable and fertile with no behavioral/neurological defects were grossly observed. More detailed behavioral/physiological characterization of homozygous mice has not been evaluated to date (April 2013).
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the Arc^CreER mouse strain in a publication, please cite the originating article(s) and include JAX stock #021881 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

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

Related Products and Services

Frozen Mouse Embryo	B6.129(Cg)-Arc<tm1.1(cre/ERT2)Luo>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129(Cg)-Arc<tm1.1(cre/ERT2)Luo>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129(Cg)-Arc<tm1.1(cre/ERT2)Luo>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129(Cg)-Arc<tm1.1(cre/ERT2)Luo>/J Frozen Embryo	$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:ArcCreER

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Arctm1.1(cre/ERT2)Luo

Allele Symbol: Arctm1.1(cre/ERT2)Luo

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Arctm1.1(cre/ERT2)Luo/Arctm1.1(cre/ERT2)Luoinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

mammalian phenotype

References

Additional References

Additional - Arctm1.1(cre/ERT2)Luo related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

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

Also Known As:Arc^CreER

Arc^{tm1.1(cre/ERT2)Luo}

Allele Symbol: Arc^{tm1.1(cre/ERT2)Luo}

Genotype: Arc^{tm1.1(cre/ERT2)Luo}/Arc^{tm1.1(cre/ERT2)Luo}
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Arc^{tm1.1(cre/ERT2)Luo} related