Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation +N1   Donating Investigator Domenico Accili,   Columbia University

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Drd3^tm1Dac mutation are viable and fertile. They show no gross anatomical or morphological changes. Dopamine antagonist binding studies indicate the absence of D3 receptors in homozygotes and a greatly reduced number in heterozygotes. Behavioral analysis of both homozygous and heterozygous mice reveals hyperactivity, increased locomotor activity and rearing behavior. Behavioral alterations were less pronounced in heterozygotes. D3 receptors are expressed in renal proximal tubules and juxtaglomerular cells and may be responsible for the dopamine-mediated decrease in renin secretion in these cells. Both systolic and diastolic blood pressures were approximately 20 mmHg higher in heterozygotes and homozygotes compared to wild-type mice.

Development
A 7 kb XhoI-Asp718 fragment was engineered for targeted mutagenesis by introducing the GKNeo cassette in antisense orientation at the SalI site in exon 2. Integration of sequences derived from the pGKNeo cassette generates a novel open reading frame, resulting in the following peptide sequence appended after Arg-148: PASDGIRTWQNNTENEVYVEQRLLISFFRL Opal (Stop). 129S4/SvJae-derived J1 embryonic stem cells were used to develop this mutant.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Drd3^tm1Dac allele

002958

B6.129S4-Drd3tm1Dac/J

View Strains carrying   Drd3^tm1Dac     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Drd3^tm1Dac/Drd3⁺

        involves: 129S4/SvJae * C57BL/6

• behavior/neurological phenotype
• decreased grooming behavior (MGI Ref ID J:32128)
  • heterozygotes tend to show reduced grooming behavior with a delayed onset; however, these differences are not statistically significant relative to wild-type grooming behavior
• hyperactivity (MGI Ref ID J:32128)
  • in the open field test, heterozygotes display hyperactivity, as shown by a 38% increase in locomotor activity (crossings) relative to wild-type mice
• increased exploration in new environment (MGI Ref ID J:32128)
  • heterozygotes exhibit increased exploratory behavior in the open field, with a degree of hyperactivity comparable to than of homozygotes during the last 11 min of a 15-min test
• increased vertical activity (MGI Ref ID J:32128)
  • in the open field test, heterozygotes display 77% more rearing episodes than wild-type mice

Drd3^tm1Dac/Drd3^tm1Dac

        involves: 129S4/SvJae * C57BL/6

• behavior/neurological phenotype
• decreased grooming behavior (MGI Ref ID J:32128)
  • homozygotes tend to show reduced grooming behavior with a delayed onset; however, these differences are not statistically significant relative to wild-type grooming behavior
• hyperactivity (MGI Ref ID J:32128)
  • in the open field test, homozygotes display hyperactivity, as shown by a 57% increase in locomotor activity (crossings) relative to wild-type mice
• increased exploration in new environment (MGI Ref ID J:32128)
  • homozygotes exhibit increased exploratory behavior in the open field test
  • in contrast, normal gait, coordination and primitive reflexes remain intact
• increased vertical activity (MGI Ref ID J:32128)
  • in the open field test, homozygotes display 93% more rearing episodes than wild-type mice

View Research Applications

Research Applications

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

Neurobiology Research
Receptor Defects (dopamine receptor)

Drd3^tm1Dac related

Cardiovascular Research
Hypertension

Neurobiology Research
Behavioral and Learning Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Drd3tm1Dac
Allele Name		targeted mutation 1, Domenico Accili
Allele Type		Targeted (knock-out)
Common Name(s)		D3-; delta148(+30);
Mutation Made By		Sara Fuchs,   National Institutes of Health
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Drd3, dopamine receptor 3
Chromosome		16
Gene Common Name(s)		D3 receptor; D3DR; D3R; ETM1; FET1; MGC149204; MGC149205;
Molecular Note		A neomycin selection cassette and sequence encoding 30 non-endogenous residues was inserted into exon 2. RT-PCR analysis on RNA derived from brain of homozygous mice demonstrated the absence of normal transcript. Mutant transcript was detected in both heterozygous and homozygous mutant mice. Binding assays on brain sections derived from homozygous mice confirmed that no functional protein was expressed. Notably, heterozygotes displayed a nearly complete loss of D3-specific binding, to a greater extentthan expected for a mutation affecting expression of one allele of the Drd3 gene, raising the possibility that this mutation acts in a dominant-negative fashion. [MGI Ref ID J:32128]

Genotyping

Genotyping Information

Genotyping Protocols

Drd3^tm1Dac, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Accili D; Fishburn CS; Drago J; Steiner H; Lachowicz JE; Park BH; Gauda EB; Lee EJ; Cool MH; Sibley DR; Gerfen CR; Westphal H; Fuchs S. 1996. A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proc Natl Acad Sci U S A 93(5):1945-9. [PubMed: 8700864]  [MGI Ref ID J:32128]

Additional References

Steiner H; Fuchs S; Accili D. 1997. D3 dopamine receptor-deficient mouse: evidence for reduced anxiety. Physiol Behav 63(1):137-41. [PubMed: 9402626]  [MGI Ref ID J:44685]

Drd3^tm1Dac related

Asico LD; Ladines C; Fuchs S; Accili D; Carey RM; Semeraro C; Pocchiari F; Felder RA; Eisner GM; Jose PA. 1998. Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension. J Clin Invest 102(3):493-8. [PubMed: 9691085]  [MGI Ref ID J:115136]

Boulay D; Depoortere R; Rostene W; Perrault G; Sanger DJ. 1999. Dopamine D3 receptor agonists produce similar decreases in body temperature and locomotor activity in D3 knock-out and wild-type mice. Neuropharmacology 38(4):555-65. [PubMed: 10221759]  [MGI Ref ID J:54420]

Boyce-Rustay JM; Risinger FO. 2003. Dopamine D3 receptor knockout mice and the motivational effects of ethanol. Pharmacol Biochem Behav 75(2):373-9. [PubMed: 12873629]  [MGI Ref ID J:102433]

Carta AR; Gerfen CR; Steiner H. 2000. Cocaine effects on gene regulation in the striatum and behavior: increased sensitivity in D3 dopamine receptor-deficient mice. Neuroreport 11(11):2395-9. [PubMed: 10943692]  [MGI Ref ID J:103704]

Clemens S; Hochman S. 2004. Conversion of the modulatory actions of dopamine on spinal reflexes from depression to facilitation in D3 receptor knock-out mice. J Neurosci 24(50):11337-45. [PubMed: 15601940]  [MGI Ref ID J:96803]

Clemens S; Sawchuk MA; Hochman S. 2005. Reversal of the circadian expression of tyrosine-hydroxylase but not nitric oxide synthase levels in the spinal cord of dopamine D3 receptor knockout mice. Neuroscience 133(2):353-7. [PubMed: 15878801]  [MGI Ref ID J:104271]

Diaz J; Pilon C; Le Foll B; Gros C; Triller A; Schwartz JC; Sokoloff P. 2000. Dopamine D3 receptors expressed by all mesencephalic dopamine neurons J Neurosci 20(23):8677-84. [PubMed: 11102473]  [MGI Ref ID J:66145]

Frances H; Le Foll B; Diaz J; Smirnova M; Sokoloff P. 2004. Role of DRD3 in morphine-induced conditioned place preference using drd3-knockout mice. Neuroreport 15(14):2245-9. [PubMed: 15371743]  [MGI Ref ID J:103701]

Karasinska JM; George SR; Cheng R; O'Dowd BF. 2005. Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation. Eur J Neurosci 22(7):1741-50. [PubMed: 16197514]  [MGI Ref ID J:102922]

Karasinska JM; George SR; El-Ghundi M; Fletcher PJ; O'Dowd BF. 2000. Modification of dopamine D(1) receptor knockout phenotype in mice lacking both dopamine D(1) and D(3) receptors. Eur J Pharmacol 399(2-3):171-81. [PubMed: 10884517]  [MGI Ref ID J:102600]

Le Foll B; Frances H; Diaz J; Schwartz JC; Sokoloff P. 2002. Role of the dopamine D3 receptor in reactivity to cocaine-associated cues in mice. Eur J Neurosci 15(12):2016-26. [PubMed: 12099907]  [MGI Ref ID J:108074]

Mizuo K; Narita M; Miyatake M; Suzuki T. 2004. Enhancement of dopamine-induced signaling responses in the forebrain of mice lacking dopamine D3 receptor. Neurosci Lett 358(1):13-6. [PubMed: 15016423]  [MGI Ref ID J:107534]

Narita M; Mizuo K; Mizoguchi H; Sakata M; Narita M; Tseng LF; Suzuki T. 2003. Molecular evidence for the functional role of dopamine D3 receptor in the morphine-induced rewarding effect and hyperlocomotion. J Neurosci 23(3):1006-12. [PubMed: 12574430]  [MGI Ref ID J:81915]

Narita M; Soma M; Tamaki H; Narita M; Suzuki T. 2002. Intensification of the development of ethanol dependence in mice lacking dopamine D(3) receptor. Neurosci Lett 324(2):129-32. [PubMed: 11988344]  [MGI Ref ID J:107932]

Short JL; Ledent C; Borrelli E; Drago J; Lawrence AJ. 2006. Genetic interdependence of adenosine and dopamine receptors: Evidence from receptor knockout mice. Neuroscience 139(2):661-70. [PubMed: 16476524]  [MGI Ref ID J:107738]

Steiner H; Fuchs S; Accili D. 1997. D3 dopamine receptor-deficient mouse: evidence for reduced anxiety. Physiol Behav 63(1):137-41. [PubMed: 9402626]  [MGI Ref ID J:44685]

Vallone D; Pignatelli M; Grammatikopoulos G; Ruocco L; Bozzi Y; Westphal H; Borrelli E; Sadile AG. 2002. Activity, non-selective attention and emotionality in dopamine D2/D3 receptor knock-out mice. Behav Brain Res 130(1-2):141-8. [PubMed: 11864730]  [MGI Ref ID J:96229]

Wong JY; Clifford JJ; Massalas JS; Finkelstein DI; Horne MK; Waddington JL; Drago J. 2003. Neurochemical changes in dopamine D1, D3 and D1/D3 receptor knockout mice. Eur J Pharmacol 472(1-2):39-47. [PubMed: 12860471]  [MGI Ref ID J:103739]

Wong JY; Clifford JJ; Massalas JS; Kinsella A; Waddington JL; Drago J. 2003. Essential conservation of D1 mutant phenotype at the level of individual topographies of behaviour in mice lacking both D1 and D3 dopamine receptors. Psychopharmacology (Berl) 167(2):167-73. [PubMed: 12652349]  [MGI Ref ID J:103886]

Zeng C; Liu Y; Wang Z; He D; Huang L; Yu P; Zheng S; Jones JE; Asico LD; Hopfer U; Eisner GM; Felder RA; Jose PA. 2006. Activation of D3 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells. Circ Res 99(5):494-500. [PubMed: 16902178]  [MGI Ref ID J:125070]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The strain is maintained by homozygous sibling matings. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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