DAT-CI mice contain the amino acid mutations L104V/F105C/A109V in exon 3 of the solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 (Slc6a3) gene. Slc6a3 encodes the dopamine transporter (DAT) which pumps the neurotransmitter dopamine out of the synapse back into cytosol. Dopamine release in the ventral tegmental area (VTA) plays a major role in reward-motivated behavior. Defects in dopamine transport reduces the rate of transport from the synapse, thus increasing the levels of dopamine in the brain. DAT has been implicated in a number of dopamine-related disorders, including attention deficit hyperactivity disorder, bipolar disorder, clinical depression, and alcoholism. Cocaine is able to block this transport, by binding directly to the DAT, increasing reward-related dopamine activity. DAT-CI mice contain a triple mutation in the transmembrane domain 2 (TM2) of the dopamine transporter introducing a conformational change on the protein structure. These mice retain a functional DAT that is rendered insensitive to cocaine. DAT-CI DAT is 70-fold more insensitive to cocaine inhibition than WT mice.
A targeting construct was designed to insert a loxP-flanked neomycin (neo) resistance cassette downstream of exon 3 of the solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 (Slc6a3) gene. The triple mutation L104V/F105C/A109V was introduced in exon 3. This targeting construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males were bred to C57BL/6J females and offspring were subsequently bred to FVB/N-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003314) to remove the floxed neo cassette. These DAT-CI mice were bred to C57BL/6J mice for at least 20 generations. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Howard H Gu|
|Allele Type||Targeted (Hypomorph, Inserted expressed sequence)|
|Gene Symbol and Name||Slc6a3, solute carrier family 6 (neurotransmitter transporter, dopamine), member 3|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A loxP-flanked neo was inserted into intron 3 with the L104V, F105C, and A109V mutations. The neo was subsequently removed from the locus.|
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129X1(FVB)-Slc6a3tm1Hhg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024165 in your Materials and Methods section.
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