Overview

Also Known As: DAT^IREScre

DAT^IREScre knock-in mice have Cre recombinase expression directed to dopaminergic neurons, without disrupting endogenous dopamine transporter expression. These mice may be useful for studying gene function in dopaminergic neurons, such as drug addiction, Parkinson's disease and Attention Deficit-Hyperactivity Disorder (ADHD).

Donating Investigator

Cristina M Backman, National Institute on Drug Abuse (NIH)

Genetic overview

Genetic Background	Generation
	N12F4 (2017-07-06 00:00:00)

Slc6a3^{tm1.1(cre)Bkmn}

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing)	Slc6a3	solute carrier family 6 (neurotransmitter transporter, dopamine), member 3

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Research Applications

Research Tools
Neurobiology Research
Cell Biology Research

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Base Price

Starting at:

$263.00 Domestic price for female 4-week

339.22 Domestic price for breeder pair

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Details

Detailed Description

Mice homozygous for this dopamine transporter IRES-cre (DAT^IREScre) knock-in allele are viable and fertile. Cre recombinase activity is observed as early as embryonic day 15, and co-localizes with endogenous gene expression in adult dopaminergic cell groups (substantia nigra (SN) and ventral tegmental area (VTA), as well as in the retrorubral field). Lesser Cre recombinase activity occurs in adult olfactory bulb glomeruli, mimicking the known lower Slc6a3 (or DAT) expression in this tissue. Although the pattern and intensity of DAT immunostaining in the SN, VTA and striatum do not differ between wild-type and mutant mice, striatum DAT protein levels are moderately reduced (17%) in heterozygotes and significantly reduced (47%) in homozygotes. This diminution in homozygous striatum is associated with significantly increased neuropeptide PDyn (but not D1, D2, or PPE) mRNA levels compared to wild-type, while such an increase is not observed in heterozygotes. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the flanked genome in dopaminergic neurons. As such, these mutant mice may be useful in neurobiological studies to facilitate the analysis of gene function in dopaminergic neurons, such as drug addiction or Parkinson's disease.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. The strain description will be modified as published results become available.

Development

To co-express both genes from the endogenous promoter (and minimize interference with endogenous gene function), a targeting vector was designed to insert an internal ribosome entry site-linked Cre recombinase gene (IRES-Cre) and FRT-flanked PGK-neo cassette 23 bp downstream from the stop codon of the endogenous gene. The construct was electroporated into C57BL/6-derived CMT2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric mice were bred to C57BL/6 mice. The FRT-flanked neo cassette was removed in the germline mice by intercrossing with a Flpe-deleter strain on a mixed B6;SJL background (see Stock No. 003800). The resulting mutant offspring (now harboring this DAT^IREScre allele) were maintained on this mixed genetic background prior to arrival at The Jackson Laboratory. Upon arrival, mice were backcrossed to the C57BL/6J inbred strain (Stock No. 000664) for at least five generations.

Expression Data

Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	Cre recombinase activity is observed as early as embryonic day 15, and co-localizes with endogenous gene expression in adult dopaminergic cell groups (substantia nigra (SN) and ventral tegmental area (VTA), as well as in the retrorubral field). Lesser Cre recombinase activity occurs in adult olfactory bulb glomeruli, mimicking the known lower Slc6a3 (or DAT) expression in this tissue.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Backman CM; Malik N; Zhang Y; Shan L; Grinberg A; Hoffer BJ; Westphal H; Tomac AC. 2006. Characterization of a mouse strain expressing Cre recombinase from the 3' untranslated region of the dopamine transporter locus. Genesis 44(8):383-90PubMed: 16865686 MGI: J:114466

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Genetics

Slc6a3^{tm1.1(cre)Bkmn}

Allele Symbol: Slc6a3^{tm1.1(cre)Bkmn}

Allele Name	targeted mutation 1.1, Cristina M Backman
Allele Type	Targeted (Recombinase-expressing)
Allele Synonym(s)	targeted mutation 1.1, Cristina M Backman; Slc6a3^{tm1.1(cre)Bkmn}
Gene Symbol and Name	Slc6a3, solute carrier family 6 (neurotransmitter transporter, dopamine), member 3
Gene Synonym(s)	DAT; dopamine transporter 1; DAT1; PKDYS; Dat1; Dat1; PKDYS1
Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	Cre recombinase activity is observed as early as embryonic day 15, and co-localizes with endogenous gene expression in adult dopaminergic cell groups (substantia nigra (SN) and ventral tegmental area (VTA), as well as in the retrorubral field). Lesser Cre recombinase activity occurs in adult olfactory bulb glomeruli, mimicking the known lower Slc6a3 (or DAT) expression in this tissue.
Strain of Origin	Not Specified
Chromosome	13
General Note	The targeting vector was electroporated into both R1 and C57BL/6 ES cells.
Molecular Note	An FRT-flanked neo was removed from the locus, leaving cre recombinase cDNA in the 3' UTR to allow bicistronic mRNA expression.
Mutations Made By	Andreas Tomac, National Institute on Drug Abuse (NIH)

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: Cre-lox System
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: Cre-lox System
- Cre-lox System
  - Cre Recombinase Expression
Neurobiology Research
- Parkinson's Disease
  - cell markers
  - strains expressing cre
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Behavioral and Learning Defects
- Cre-lox System
  - Cre Recombinase expression in neural tissue
- Channel and Transporter Defects
Cell Biology Research
- Channel and Transporter Defects

Genotype: Slc6a3^{tm1.1(cre)Bkmn} related

Neurobiology Research
- Parkinson's Disease
  - strains expressing cre

Mammalian Phenotype Terms by Genotype

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

Genotype: Slc6a3^{tm1.1(cre)Bkmn}/Slc6a3^{tm1.1(cre)Bkmn}
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

normal phenotype

no abnormal phenotype detected
- Normal - homozygous and heterozygous mice are normal and viable

References

Backman CM; Malik N; Zhang Y; Shan L; Grinberg A; Hoffer BJ; Westphal H; Tomac AC. 2006. Characterization of a mouse strain expressing Cre recombinase from the 3' untranslated region of the dopamine transporter locus. Genesis 44(8):383-90PubMed: 16865686 MGI: J:114466

Additional - Slc6a3^{tm1.1(cre)Bkmn} related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Slc6a3^{tm1.1(cre)Bkmn}
- SEPARATED MELT: Slc6a3^{tm1.1(cre)Bkmn}
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, heterozygous mice are bred to wildtype siblings or to inbred C57BL/6J (Stock No. 000664). Homozygous mice have approximately half of the endogenous gene expression associated with altered neuropeptide levels in the brain, while heterozygotes have a moderate, non-significant reduction in endogenous gene expression with no reported neuropeptide abnormalities.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the DAT^IREScre mouse strain in a publication, please cite the originating article(s) and include JAX stock #006660 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Repository Live

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service	Genotype	Price
	heterozygous or Wild-Type for Slc6a3<tm1.1(cre)Bkmn>

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.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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Licensing Information

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Also Known As: DATIREScre

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Slc6a3tm1.1(cre)Bkmn

Allele Symbol: Slc6a3tm1.1(cre)Bkmn

Disease Terms

Research Areas By Genotype

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

Genotype: Slc6a3tm1.1(cre)Bkmn related

Mammalian Phenotype Terms by Genotype

Genotype: Slc6a3tm1.1(cre)Bkmn/Slc6a3tm1.1(cre)Bkmninvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

normal phenotype

References

Additional - Slc6a3tm1.1(cre)Bkmn related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

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: DAT^IREScre

Slc6a3^{tm1.1(cre)Bkmn}

Allele Symbol: Slc6a3^{tm1.1(cre)Bkmn}

Genotype: Slc6a3^{tm1.1(cre)Bkmn} related

Genotype: Slc6a3^{tm1.1(cre)Bkmn}/Slc6a3^{tm1.1(cre)Bkmn}
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Slc6a3^{tm1.1(cre)Bkmn} related