Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +N1 Generation Definitions   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)

Strains carrying other alleles of Drd3

002958

B6.129S4-Drd3tm1Dac/J

View Strains carrying other alleles of Drd3     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Drd3^tm1Dac/Drd3⁺

        involves: 129S4/SvJae * C57BL/6

• behavior/neurological phenotype
• abnormal locomotor activation
  • during the first part of the test (increased early and decreased late) unlike wild-type mice   (MGI Ref ID J:96229)
• • hyperactivity
    • in the open field test, heterozygotes display hyperactivity, as shown by a 38% increase in locomotor activity (crossings) relative to wild-type mice   (MGI Ref ID J:32128)
    • during the first part of the test   (MGI Ref ID J:96229)
  • increased vertical activity
    • in the open field test, heterozygotes display 77% more rearing episodes than wild-type mice   (MGI Ref ID J:32128)
    • during the first part of the test   (MGI Ref ID J:96229)
• decreased grooming behavior
  • heterozygotes tend to show reduced grooming behavior with a delayed onset; however, these differences are not statistically significant relative to wild-type grooming behavior   (MGI Ref ID J:32128)
• increased exploration in new environment
  • 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   (MGI Ref ID J:32128)
• cardiovascular system phenotype
• increased systemic arterial diastolic blood pressure
  • after anesthesia with pentobarbital   (MGI Ref ID J:115136)
• increased systemic arterial systolic blood pressure
  • after anesthesia with pentobarbital   (MGI Ref ID J:115136)
• homeostasis/metabolism phenotype
• increased renin activity   (MGI Ref ID J:115136)

Drd3^tm1Dac/Drd3⁺

        involves: 129S4/SvJae * C57BL/6J

• behavior/neurological phenotype
• decreased anxiety-related response
  • mice exhibit moderately more time in the center of the open field and with the open arms of an elevated plus maze compared with wild-type mice   (MGI Ref ID J:44685)

Drd3^tm1Dac/Drd3^tm1Dac

        involves: 129S4/SvJae * C57BL/6

• behavior/neurological phenotype
• decreased grooming behavior
  • homozygotes tend to show reduced grooming behavior with a delayed onset; however, these differences are not statistically significant relative to wild-type grooming behavior   (MGI Ref ID J:32128)
• hyperactivity
  • in the open field test, homozygotes display hyperactivity, as shown by a 57% increase in locomotor activity (crossings) relative to wild-type mice   (MGI Ref ID J:32128)
• impaired behavioral response to morphine
  • mice exhibit decreased morphine-induced conditioned place preference (CPP) compared with similarly treated wild-type mice   (MGI Ref ID J:103701)
  • BP 897-treated mice fail to exhibit a decrease in morphine-induced CPP compared with similarly treated wild-type mice   (MGI Ref ID J:103701)
• impaired conditioned place preference behavior
  • mice exhibit decreased morphine-induced conditioned place preference (CPP) compared with similarly treated wild-type mice   (MGI Ref ID J:103701)
  • BP 897-treated mice fail to exhibit a decrease in morphine-induced CPP compared with similarly treated wild-type mice   (MGI Ref ID J:103701)
• increased exploration in new environment
  • homozygotes exhibit increased exploratory behavior in the open field test   (MGI Ref ID J:32128)
  • in contrast, normal gait, coordination and primitive reflexes remain intact   (MGI Ref ID J:32128)
• increased vertical activity
  • in the open field test, homozygotes display 93% more rearing episodes than wild-type mice   (MGI Ref ID J:32128)
• cardiovascular system phenotype
• decreased systemic arterial systolic blood pressure
  • systolic blood pressure in losartan-treated mice remains depressed longer than similarly treated wild-type mice   (MGI Ref ID J:115136)
• increased systemic arterial diastolic blood pressure
  • after anesthesia with pentobarbital   (MGI Ref ID J:115136)
• increased systemic arterial systolic blood pressure
  • after anesthesia with pentobarbital   (MGI Ref ID J:115136)
• homeostasis/metabolism phenotype
• abnormal physiological response to xenobiotic
  • systolic blood pressure in losartan-treated mice remains depressed longer than similarly treated wild-type mice   (MGI Ref ID J:115136)
• decreased urine sodium level
  • after acute saline loading   (MGI Ref ID J:115136)
• increased renin activity
  • in the kidneys   (MGI Ref ID J:115136)
• renal/urinary system phenotype
• decreased urine flow rate
  • after acute saline loading, urine flow is decreased compared to in wild-type mice   (MGI Ref ID J:115136)
• decreased urine sodium level
  • after acute saline loading   (MGI Ref ID J:115136)

Drd3^tm1Dac/Drd3^tm1Dac

        involves: 129S4/SvJae * C57BL/6J

• behavior/neurological phenotype
• decreased anxiety-related response
  • mice exhibit more time in the center of the open field and with the open arms of an elevated plus maze compared with wild-type mice   (MGI Ref ID J:44685)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Drd3^tm1Dac/Drd3^tm1Dac

        B6.129S4-Drd3^tm1Dac/J

• behavior/neurological phenotype
• abnormal motor coordination/ balance
  • on day 2, mice exhibit improved performance on a rotarod compared with wild-type mice   (MGI Ref ID J:102600)
• abnormal reflex
  • mice exhibit more large-reflex amplitudes for both monosynaptic 'stretch' reflex (MSR) and longer-latency reflex responses compared with wild-type mice   (MGI Ref ID J:96803)
  • mice treated with 1 or 5 um dopamine exhibit led to an increase in MSR amplitude and reflex strength unlike in similarly treated wild-type mice   (MGI Ref ID J:96803)
  • mice treated with a D3 receptor antagonist do not exhibit an increase in monosynaptic reflex strength unlike in similarly treated wild-type mice   (MGI Ref ID J:96803)
  • mice treated with D2 receptor agonists fail to exhibit a decrease in monosynaptic reflex strength compared with similarly treated wild-type mice   (MGI Ref ID J:96803)
  • mice treated with pergolide do not exhibit a difference in monosynaptic and longer-latency reflex amplitudes unlike in similarly treated wild-type mice   (MGI Ref ID J:96803)
  • mice treated with GR 103691 exhibit shorter monosynaptic than longer-latency reflex amplitude unlike in wild-type mice   (MGI Ref ID J:96803)
• decreased anxiety-related response
  • mice exhibit increased entry into open arms in an elevated plus maze compared with wild-type mice   (MGI Ref ID J:102600)
• hyperactivity
  • in an open field compared with wild-type mice   (MGI Ref ID J:102600)
• increased vertical activity   (MGI Ref ID J:102600)
• homeostasis/metabolism phenotype
• abnormal physiological response to xenobiotic
  • mice treated with a D3 receptor antagonist do not exhibit an increase in monosynaptic reflex strength unlike in similarly treated wild-type mice   (MGI Ref ID J:96803)
  • mice treated with D2 receptor agonists fail to exhibit a decrease in monosynaptic reflex strength compared with similarly treated wild-type mice   (MGI Ref ID J:96803)
  • mice treated with pergolide do not exhibit a difference in monosynaptic and longer-latency reflex amplitudes unlike in similarly treated wild-type mice   (MGI Ref ID J:96803)
  • mice treated with GR 103691 exhibit shorter monosynaptic than longer-latency reflex amplitude unlike in wild-type mice   (MGI Ref ID J:96803)

Drd3^tm1Dac/Drd3^tm1Dac

        involves: 129S4/SvJae

• behavior/neurological phenotype
• abnormal behavioral response to addictive substance
  • mice treated with cocaine exhibit reduced hyperactivity and increased head bobbing compared with similarly treated wild-type mice   (MGI Ref ID J:103704)
• • enhanced behavioral response to alcohol
    • after a single injection of ethanol, mice exhibit reduced onset time to sleep and longer sleep time compared with similarly treated wild-type mice   (MGI Ref ID J:107932)
  • increased behavioral withdrawal response
    • 3 and 6 hours after discontinuation of ethanol treatment, mice exhibit increased levels of withdrawal scores compared with similarly treated wild-type mice   (MGI Ref ID J:107932)
    • however, withdrawal scores at 12 and 18 hours are normal   (MGI Ref ID J:107932)
• decreased alcohol consumption
  • during chronic ethanol treatment   (MGI Ref ID J:107932)
• head bobbing
  • cocaine-treated mice exhibit increased head bobbing compared with similarly treated wild-type mice   (MGI Ref ID J:103704)
• hypoactivity
  • 5 days after cocaine treatment, mice exhibit less induced locomotion compared with similarly treated wild-type mice   (MGI Ref ID J:103704)

Drd3^tm1Dac/Drd3^tm1Dac

        B6.129S4-Drd3^tm1Dac

• behavior/neurological phenotype
• decreased startle reflex
  • mice exhibit reduced acoustic startle response amplitude compared with wild-type mice   (MGI Ref ID J:154428)

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 provided by MGI

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 D3
Chromosome		16
Gene Common Name(s)		D3 receptor; D3DR; D3R; ETM1; FET1;
General Note		Phenotypic Similarity to Human Syndrome: Restless Leg Syndrome (J:96803)
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, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Dowling P; Klinker F; Stadelmann C; Hasan K; Paulus W; Liebetanz D. 2011. Dopamine D3 receptor specifically modulates motor and sensory symptoms in iron-deficient mice. J Neurosci 31(1):70-7. [PubMed: 21209191]  [MGI Ref ID J:167855]

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]

Halberstadt AL; Geyer MA. 2009. Habituation and sensitization of acoustic startle: opposite influences of dopamine D1 and D2-family receptors. Neurobiol Learn Mem 92(2):243-8. [PubMed: 18644244]  [MGI Ref ID J:154428]

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]

Klinker F; Hasan K; Dowling P; Paulus W; Liebetanz D. 2011. Dopamine D(3) receptor deficiency sensitizes mice to iron deficiency-related deficits in motor learning. Behav Brain Res 220(2):358-61. [PubMed: 21354213]  [MGI Ref ID J:171457]

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]

Maison SF; Liu XP; Eatock RA; Sibley DR; Grandy DK; Liberman MC. 2012. Dopaminergic Signaling in the Cochlea: Receptor Expression Patterns and Deletion Phenotypes. J Neurosci 32(1):344-355. [PubMed: 22219295]  [MGI Ref ID J:179360]

Marcellino D; Ferre S; Casado V; Cortes A; Le Foll B; Mazzola C; Drago F; Saur O; Stark H; Soriano A; Barnes C; Goldberg SR; Lluis C; Fuxe K; Franco R. 2008. Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum. J Biol Chem 283(38):26016-25. [PubMed: 18644790]  [MGI Ref ID J:141997]

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

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

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 Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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