DATIREScre 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).
Cristina M Backman, National Institute on Drug Abuse (NIH)
Genetic Background | Generation |
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N12F5
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Recombinase-expressing) | Slc6a3 | solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 |
Starting at:
$270.00 Domestic price for female 4-week |
348.51 Domestic price for breeder pair |
Mice homozygous for this dopamine transporter IRES-cre (DATIREScre) 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.
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 (Stock No. 000664) for at least five generations.
Expressed Gene | cre, cre recombinase, bacteriophage P1 |
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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. |
Allele Name | targeted mutation 1.1, Cristina M Backman |
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Allele Type | Targeted (Recombinase-expressing) |
Allele Synonym(s) | DatIRESCre; DatIREScre; DATCre; DAT-IRES-Cre |
Gene Symbol and Name | Slc6a3, solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 |
Gene Synonym(s) | |
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) |
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.
When using the DATIREScre mouse strain in a publication, please cite the originating article(s) and include JAX stock #006660 in your Materials and Methods section.
Service/Product | Description | Price |
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heterozygous or Wild-Type for Slc6a3<tm1.1(cre)Bkmn> |
Frozen Mouse Embryo | B6.SJL-Slc6a3tm1.1(cre)Bkmn/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.SJL-Slc6a3tm1.1(cre)Bkmn/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.SJL-Slc6a3tm1.1(cre)Bkmn/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6.SJL-Slc6a3tm1.1(cre)Bkmn/J Frozen Embryos | $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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