These D4R-mutant mice harbor a dopamine receptor 4 (Drd4; also called dopamine D4 receptor (D4R)) targeted mutation where exon 2 is replaced with a neomycin resistance cassette, and may be useful in studying dopamine/neurotransmitter function, drug addiction, Parkinson's disease, and schizophrenia or other psychoses.
Dr. Malcolm J Low, University of Michigan Medical School
Mice homozygous for this targeted mutation (D4R-/-) are viable and fertile. With exon 2 of the mutant locus deleted, the truncated transcript is predicted to produce a 131 amino acid mutant polypeptide. Homozygous mice may exhibit locomotor supersensitivity to ethanol, cocaine, and methamphetamine, as well as alterations in dopamine synthesis and function, glutamate levels and metabolism, behavioral responses to novelty, and spontaneous locomotor activity in both novel and familiar environments. These D4R-mutant mice may be useful in studying dopamine/neurotransmitter function, drug addiction, Parkinson's disease, and schizophrenia or other psychoses.
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. We will modify the strain description if necessary as published results become available.
A targeting vector was designed to replace exon 2 of the targeted gene with a neomycin resistance cassette. The construct was electroporated into 129P2/OlaHsd-derived E14TG2A embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred to C57BL/6J females. Heterozygous D4R-mutant mice were bred to wildtype siblings or C57BL/6J mice for approximately 30 generations (including to C57BL/6J for 5 most recent generations) prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, David K Grandy|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||D4-; D4KO; D4R -; Drd4-|
|Gene Symbol and Name||Drd4, dopamine receptor D4|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A neomycin resistance cassette replaced exon 2. RT-PCR analysis demonstrated that a mutated transcript was produced from this allele that spliced exon 1 to exon 3. This mutation causes a shift in the reading frame that is predicted to result in the production of a truncated protein.|
|Mutations Made By|| |
David Grandy, Oregon Heath Sciences University
When maintaining a live colony, homozygous mice may be bred together.
When using the Drd4- mouse strain in a publication, please cite the originating article(s) and include JAX stock #008084 in your Materials and Methods section.