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| These dopamine transporter IRES-cre (DATIREScre) mutant mice exhibit co-localization of Cre recombinase and endogenous Slc6a3 (solute carrier family 6 (neurotransmitter transporter, dopamine), member 3) gene expression and may be useful in neurobiological studies to facilitate the analysis of gene function in dopaminergic neurons, such as drug addiction or Parkinson's disease. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
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Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System +/+ sibling x Heterozygote (Female x Male) 16-DEC-08 Species laboratory mouse Generation N10 (27-OCT-09) Donating Investigator IMR Colony, The Jackson Laboratory Description
Mice homozygous for this dopamine transporter IRES-cre (DATIREScre) mutant 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 DATIREScre 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 for at least five generations.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Slc6a3
009090 FVB/NJ-Tg(Slc6a3-PARK2*Q311X)AXwy/J View Strains carrying other alleles of Slc6a3 (1 strain)
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.
Slc6a3tm1.1(cre)Bkmn/Slc6a3tm1.1(cre)Bkmn
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
- normal phenotype
- no abnormal phenotype detected (MGI Ref ID J:114466)
- homozygous and heterozygous mice are normal and viable
This mouse can be used to support research in many areas including:
cre relatedCell Biology Research
Channel and Transporter Defects
Neurobiology Research
Behavioral and Learning Defects
Channel and Transporter Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Research Tools
Cre-lox System
Cre Recombinase Expression
Cre Recombinase Expression: Germline/Embryonic Expression
Genetics Research
Mutagenesis and Transgenesis: Cre-lox System
Slc6a3tm1.1(cre)Bkmn relatedResearch Tools
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis: Cre-lox System
Neurobiology Research
Parkinson's Disease
strains expressing cre
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Slc6a3tm1.1(cre)Bkmn | ||
|---|---|---|---|
| Allele Name | targeted mutation 1.1, Cristina M Backman | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | DatIREScre; | ||
| Mutation Made By | Andreas Tomac, National Institute on Drug Abuse (NIH) | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| 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. | ||
| 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. | |||
| Gene Symbol and Name | Slc6a3, solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 | ||
| Chromosome | 13 | ||
| Gene Common Name(s) | DAT; DAT1; Dat1; dopamine transporter 1; | ||
| Driver Note | Slc6a3 | ||
| General Note | S cells or C57BL/6 ES cells were used. | ||
| Molecular Note | An FRT-flanked neo was removed from the locus, leaving cre recombinase cDNA in the 3' UTR to allow bicistronic mRNA expression. C57BL/6 ES cells were also used. [MGI Ref ID J:114466] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Slc6a3tm1.1(cre)Bkmn, Melt Curve Analysis
Slc6a3tm1.1(cre)Bkmn, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
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):383-90. [PubMed: 16865686] [MGI Ref ID J:114466]
Additional References
Slc6a3tm1.1(cre)Bkmn relatedDiaz-Ruiz O; Zapata A; Shan L; Zhang Y; Tomac AC; Malik N; de la Cruz F; Backman CM. 2009. Selective deletion of PTEN in dopamine neurons leads to trophic effects and adaptation of striatal medium spiny projecting neurons. PLoS One 4(9):e7027. [PubMed: 19750226] [MGI Ref ID J:153622]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry 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. Mating System +/+ sibling x Heterozygote (Female x Male) 16-DEC-08
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $243.50 Female or Male Heterozygous for Slc6a3tm1.1(cre)Bkmn
Pairs /Price (US dollars $) Pair Genotype $297.85 Heterozygous for Slc6a3tm1.1(cre)Bkmn x Wild-type for Slc6a3tm1.1(cre)Bkmn $297.85 Wild-type for Slc6a3tm1.1(cre)Bkmn x Heterozygous for Slc6a3tm1.1(cre)Bkmn
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $316.60 Female or Male Heterozygous for Slc6a3tm1.1(cre)Bkmn
Pairs /Price (US dollars $) Pair Genotype $387.30 Heterozygous for Slc6a3tm1.1(cre)Bkmn x Wild-type for Slc6a3tm1.1(cre)Bkmn $387.30 Wild-type for Slc6a3tm1.1(cre)Bkmn x Heterozygous for Slc6a3tm1.1(cre)Bkmn
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering and Purchasing Information
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