In this knockin strain, the inserted dominant negative N616R mutation of the NR1 subunit of NMDA receptor (Grin1) is expressed in all brain cells that normally express the dopamine D1 receptor (D1R, Drd1a), including the striatum. Mice expressing the mutant NMDA receptors in D1R-containing cells have normal basal activity and display similar increases in locomotor activity when treated with acute amphetamine or cocaine. However, the mutant mice fail to display locomotor sensitization to repeated cocaine administration. In addition, these mice also have a decreased ability to form a conditioned place preference to cocaine.
Dr. Richard Palmiter, University of Washington
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Dominant negative) | Drd1 | dopamine receptor D1 |
In this knockin strain, the inserted dominant negative N616R mutation of the NR1 subunit of NMDA receptor (Grin1) is expressed in all brain cells that normally express the dopamine D1 receptor (D1R, Drd1a), including the striatum. Mice expressing the mutant NMDA receptors in D1R-containing cells have normal basal activity and display similar increases in locomotor activity when treated with acute amphetamine or cocaine. However, the mutant mice fail to display locomotor sensitization to repeated cocaine administration. In addition, these mice also have a decreased ability to form a conditioned place preference to cocaine. Homozygotes are small and some die prior to weaning. Heterozygous mice are normal in most respects, however they manifest blunted sensitization to cocaine and there are subtle differences in their conditioned place preference to cocaine.
A targeting vector was designed to insert a Grin1 (NR1) cDNA open reading frame (including an HA-epitope tag, N616R mutation, and floxed neomycin resistance gene) just upstream of the normal initiation site of the Drd1a gene. The vector was introduced to (C57BL/6J x 129S4/SvJae)F1-derived V6.4 embryonic stem (ES) cells. This line has been minimally backcrossed to C57BL/6 by the donating laboratory.
Expressed Gene | Grin1, glutamate receptor, ionotropic, NMDA1 (zeta 1), mouse, laboratory |
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Site of Expression |
Allele Name | targeted mutation 1, Richard D Palmiter |
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Allele Type | Targeted (Dominant negative) |
Allele Synonym(s) | D1R-NR1m; Drd1aGrin1-N616R; Drd1adnNR1 |
Gene Symbol and Name | Drd1, dopamine receptor D1 |
Gene Synonym(s) | |
Expressed Gene | Grin1, glutamate receptor, ionotropic, NMDA1 (zeta 1), mouse, laboratory |
Strain of Origin | (C57BL/6J x 129S4/SvJae)F1 |
Chromosome | 13 |
Molecular Note | A cDNA open reading frame encoding a dominant-negative mutant NR1 subunit of the NMDA receptor with an asparagine-to-arginine substitution at amino acid 616 (N616R), a hemagglutinin (HA) epitope tag 27 aa from the N terminus and a polyadenylation signal, followed by a loxP-flanked SV40-neo cassette, has replaced the first ~130 base pairs of the endogenous Drd1a gene. |
Mutations Made By | Dr. Richard Palmiter, University of Washington |
When maintaining a live colony, these mice are bred as heterozygotes.
When using the B6;129S4-Drd1tm2Rpa/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007586 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or Wild-type for Drd1a<tm2Rpa> |
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