Overview

Also Known As:D3R KO

These Drd3 knockout mice exhibit altered responses to cocaine (D1 agonist) and amphetamine (D2 agonist) administered separately and together. This strain may be useful for studying dopamine neurotransmission.

Donating Investigator

Ming Xu, University of Chicago

Genetic overview

Genetic Background	Generation

Drd3^tm1Stl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Drd3	dopamine receptor D3

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Research Applications

Neurobiology Research

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Details

Detailed Description

Drd3 (dopamine receptor D3) is a G-protein coupled receptor expressed in the limbic system and involved in adenylyl cyclase inhibition. D3 is associated with motor and reward-related behavior. Mice homozygous for this knockout allele are viable and fertile. Drd3-deficient mice exhibit a transient increase in activity in a novel environment, increased activity at low, but not high, doses of cocaine, an altered sensitivity to amphetamine in the conditioned cue preference (CCP) test and enhanced behavioral sensitivity to a combined injection of cocaine and amphetamines (D1 and D2 agonists). This strain may be useful for studying dopamine neurotransmission

Development

A targeting vector containing a PGKneo cassette was used to replace exon 1. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 and offspring were backcrossed to C57BL/6 for 2 generations. Upon arrival, mice were bred to C57BL/6J mice (Stock No. 000664) for at least 1 generation to establish the colony.

Control Suggestions

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Xu M; Koeltzow TE; Santiago GT; Moratalla R; Cooper DC; Hu XT ; White NM ; Graybiel AM ; White FJ ; Tonegawa S. 1997. Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors. Neuron 19(4):837-48PubMed: 9354330 MGI: J:43791

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Genetics

Drd3^tm1Stl

Allele Symbol: Drd3^tm1Stl

Allele Name	targeted mutation 1, Susumu Tonegawa
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	D3^-; D3R KO; D3R^-
Gene Symbol and Name	Drd3, dopamine receptor D3
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	16
Molecular Note	A PGK-neo cassette replaced exon 1. Southern blot analysis confirmed recombination. Autoradiographic analysis confirmed the absence of Drd3 binding sites in brains of homozygous mice.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Receptor Defects
  - dopamine receptor

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Drd3^tm1Stl/Drd3^tm1Stl
involves: 129S2/SvPas * C57BL/6

adipose tissue phenotype

increased percent body fat/body weight
- female mutants on a high fat diet display a significant increase in percent body fat compared to female wild-type littermates

increased total body fat amount
- homozygous mice on a high fat diet have significantly increased body fat unlike wild-type mice

behavior/neurological phenotype

abnormal cued conditioning behavior
- male homozygous mice display a significant preference for amphetamines at lower concentrations compared to their male wild-type littermates

abnormal food intake
- only male mutants had a detectable increase in caloric consumption on a high fat diet

hyperactivity
- male homozygous mice display a greater increase in activity with low doses of cocaine compared to male wild-type littermates

increased exploration in new environment
- male homozygous mice display increased activity during the first 5 minutes in a novel environment compared to male wild-type littermates

growth/size/body region phenotype

abnormal body water content
- male mutants on a high fat diet display a significant increase in water content compared to male wild-type littermates

increased susceptibility to weight gain
- male mutants on a high fat diet have a significant increase in body weight compared to male wild-type littermates or male mutants on a regular diet

homeostasis/metabolism phenotype

increased circulating leptin level
- on a high fat diet plasma leptin is significantly increased in male mutants but not in their male wild-type littermates
- plasma leptin is increased on both the normal chow and high fat diets in female mutants compared to female wild-type littermates

References

Xu M; Koeltzow TE; Santiago GT; Moratalla R; Cooper DC; Hu XT ; White NM ; Graybiel AM ; White FJ ; Tonegawa S. 1997. Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors. Neuron 19(4):837-48PubMed: 9354330 MGI: J:43791

Additional - Drd3^tm1Stl related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Drd3
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the D3R KO mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37114 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

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Questions about Terms of Use

Licensing Information

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Also Known As:D3R KO

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Drd3tm1Stl

Allele Symbol: Drd3tm1Stl

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Drd3tm1Stl/Drd3tm1Stlinvolves: 129S2/SvPas * C57BL/6

adipose tissue phenotype

behavior/neurological phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional - Drd3tm1Stl related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Drd3^tm1Stl

Allele Symbol: Drd3^tm1Stl

Genotype: Drd3^tm1Stl/Drd3^tm1Stl
involves: 129S2/SvPas * C57BL/6

Additional - Drd3^tm1Stl related