Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S2 via D3 ES cell line Generation N11 (26-FEB-06)   Donating Investigator Malcolm Low,   Oregon Health Sciences University

Description
Mice with a disrupted D2 dopamine receptor gene display chronic hyperprolactinemia and develop anterior lobe lactotrophhyperplasia without evidence of adenomatous transformation. Homozygous mutant mice have no hyperplasia of the intermediate lobe melanotrophs. Aged female D2 receptor homozygous mice develop uterine adenomyosis in response to prolonged prolactin exposure. They also exhibit a locomotor deficit manifested as a 50% reduction in activity and decreased initiation of movement. Female homozygous mice develop prolactinomas of the anterior pituitary gland. Homozygous mice exhibit decreased sensitivity to the rewarding and locomotor effects of ethanol. Drd2^tm1Low mice may provide a model for Parkinson's disease.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Drd2^tm1Low/Drd2^tm1Low

        involves: 129 * C57BL/6

• behavior/neurological phenotype
• abnormal locomotor activation (MGI Ref ID J:102700)
  • mutants do not show lower levels of locomotor stimulation in response to a Grm5 antagonist, MPEP, whereas compared to wild-type controls

View Research Applications

Research Applications

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

Neurobiology Research
Parkinson's Disease
Receptor Defects (dopamine receptor)

Drd2^tm1Low related

Neurobiology Research
Receptor Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Drd2tm1Low
Allele Name		targeted mutation 1, Malcolm J Low
Allele Type		Targeted (knock-out)
Common Name(s)		D2 KO; D2-; D2KO; Drd2-;
Mutation Made By		Malcolm Low,   Oregon Health Sciences University
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Drd2, dopamine receptor 2
Chromosome		9
Gene Common Name(s)		D2 receptor; D2DR; D2R; Drd-2; dopamine D2 receptor;
Inducible Note		J:134260 used Jax mice.
Molecular Note		A genomic fragment containing exon 7 and part of exon 8 was replaced by a neomycin resistance cassette. [MGI Ref ID J:41858]

Genotyping

Genotyping Information

Genotyping Protocols

Drd2^tm1Low, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Kelly MA; Rubinstein M; Asa SL; Zhang G; Saez C; Bunzow JR; Allen RG ; Hnasko R ; Ben-Jonathan N ; Grandy DK ; Low MJ. 1997. Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice. Neuron 19(1):103-13. [PubMed: 9247267]  [MGI Ref ID J:41858]

Additional References

Drd2^tm1Low related

Asa SL; Kelly MA; Grandy DK; Low MJ. 1999. Pituitary lactotroph adenomas develop after prolonged lactotroph hyperplasia in dopamine D2 receptor-deficient mice. Endocrinology 140(11):5348-55. [PubMed: 10537166]  [MGI Ref ID J:58342]

Cepeda C; Hurst RS; Altemus KL; Flores-Hernandez J; Calvert CR; Jokel ES; Grandy DK; Low MJ; Rubinstein M; Ariano MA; Levine MS. 2001. Facilitated glutamatergic transmission in the striatum of D2 dopamine receptor-deficient mice. J Neurophysiol 85(2):659-70. [PubMed: 11160501]  [MGI Ref ID J:103965]

Chakroborty D; Chowdhury UR; Sarkar C; Baral R; Dasgupta PS; Basu S. 2008. Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization. J Clin Invest 118(4):1380-9. [PubMed: 18340382]  [MGI Ref ID J:135975]

Chausmer AL; Elmer GI; Rubinstein M; Low MJ; Grandy DK; Katz JL. 2002. Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2 receptor mutant mice. Psychopharmacology (Berl) 163(1):54-61. [PubMed: 12185400]  [MGI Ref ID J:103795]

Chen JF; Moratalla R; Impagnatiello F; Grandy DK; Cuellar B; Rubinstein M; Beilstein MA; Hackett E; Fink JS; Low MJ; Ongini E; Schwarzschild MA. 2001. The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice. Proc Natl Acad Sci U S A 98(4):1970-5. [PubMed: 11172060]  [MGI Ref ID J:67550]

Clifford JJ; Kinsella A; Tighe O; Rubinstein M; Grandy DK; Low MJ; Croke DT; Waddington JL. 2001. Comparative, topographically-based evaluation of behavioural phenotype and specification of D(1)-like:D(2) interactions in a line of incipient congenic mice with D(2) dopamine receptor 'knockout'. Neuropsychopharmacology 25(4):527-36. [PubMed: 11557166]  [MGI Ref ID J:106290]

Crandall JE; McCarthy DM; Araki KY; Sims JR; Ren JQ; Bhide PG. 2007. Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex. J Neurosci 27(14):3813-22. [PubMed: 17409246]  [MGI Ref ID J:121219]

Cristina C; Diaz-Torga G; Baldi A; Gongora A; Rubinstein M; Low MJ; Becu-Villalobos D. 2005. Increased pituitary vascular endothelial growth factor-a in dopaminergic D2 receptor knockout female mice. Endocrinology 146(7):2952-62. [PubMed: 15817666]  [MGI Ref ID J:129824]

Cristina C; Diaz-Torga G; Gongora A; Guida MC; Perez-Millan MI; Baldi A; Becu-Villalobos D. 2007. Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice. Am J Physiol Endocrinol Metab 293(5):E1341-51. [PubMed: 17848635]  [MGI Ref ID J:129379]

Cristina C; Diaz-Torga GS; Goya RG; Kakar SS; Perez-Millan MI; Passos VQ; Giannella-Neto D; Bronstein MD; Becu-Villalobos D. 2007. PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes. Mol Cancer 6:4. [PubMed: 17222350]  [MGI Ref ID J:121484]

Cunningham CL; Howard MA; Gill SJ; Rubinstein M; Low MJ; Grandy DK. 2000. Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice. Pharmacol Biochem Behav 67(4):693-9. [PubMed: 11166059]  [MGI Ref ID J:102654]

Diaz-Torga G; Feierstein C; Libertun C; Gelman D; Kelly MA; Low MJ; Rubinstein M; Becu-Villalobos D. 2002. Disruption of the D2 dopamine receptor alters GH and IGF-I secretion and causes dwarfism in male mice. Endocrinology 143(4):1270-9. [PubMed: 11897683]  [MGI Ref ID J:106832]

Dockstader CL; Rubinstein M; Grandy DK; Low MJ; van der Kooy D. 2001. The D2 receptor is critical in mediating opiate motivation only in opiate-dependent and withdrawn mice. Eur J Neurosci 13(5):995-1001. [PubMed: 11264672]  [MGI Ref ID J:75904]

Dracheva S; Haroutunian V. 2001. Locomotor behavior of dopamine D1 receptor transgenic/D2 receptor deficient hybrid mice. Brain Res 905(1-2):142-51. [PubMed: 11423089]  [MGI Ref ID J:70357]

Elmer GI; Pieper JO; Levy J; Rubinstein M; Low MJ; Grandy DK; Wise RA. 2005. Brain stimulation and morphine reward deficits in dopamine D2 receptor-deficient mice. Psychopharmacology (Berl) 182(1):33-44. [PubMed: 16136297]  [MGI Ref ID J:114311]

Fowler SC; Zarcone TJ; Vorontsova E; Chen R. 2002. Motor and associative deficits in D2 dopamine receptor knockout mice. Int J Dev Neurosci 20(3-5):309-21. [PubMed: 12175868]  [MGI Ref ID J:100036]

Hayward MD; Low MJ. 2005. Naloxone's suppression of spontaneous and food-conditioned locomotor activity is diminished in mice lacking either the dopamine D(2) receptor or enkephalin. Brain Res Mol Brain Res 140(1-2):91-8. [PubMed: 16125819]  [MGI Ref ID J:124309]

Hentges ST; Low MJ. 2002. Ovarian dependence for pituitary tumorigenesis in d2 dopamine receptor-deficient mice. Endocrinology 143(12):4536-43. [PubMed: 12446580]  [MGI Ref ID J:80287]

Huey KA; Low MJ; Kelly MA; Juarez R; Szewczak JM; Powell FL. 2000. Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D(2) receptors. J Appl Physiol 89(3):1142-50. [PubMed: 10956362]  [MGI Ref ID J:130701]

Ito M; Numachi Y; Ohara A; Sora I. 2008. Hyperthermic and lethal effects of methamphetamine: Roles of dopamine D1 and D2 receptors. Neurosci Lett 438(3):327-9. [PubMed: 18486343]  [MGI Ref ID J:137069]

Kachroo A; Orlando LR; Grandy DK; Chen JF; Young AB; Schwarzschild MA. 2005. Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice. J Neurosci 25(45):10414-9. [PubMed: 16280580]  [MGI Ref ID J:102700]

Kelly MA; Rubinstein M; Phillips TJ; Lessov CN; Burkhart-Kasch S; Zhang G; Bunzow JR; Fang Y; Gerhardt GA; Grandy DK; Low MJ. 1998. Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene dosage, genetic background, and developmental adaptations. J Neurosci 18(9):3470-9. [PubMed: 9547254]  [MGI Ref ID J:47001]

Kruzich PJ; Grandy DK. 2004. Dopamine D2 receptors mediate two-odor discrimination and reversal learning in C57BL/6 mice. BMC Neurosci 5(1):12. [PubMed: 15061865]  [MGI Ref ID J:90593]

Kuchenbauer F; Theodoropoulou M; Hopfner U; Stalla J; Renner U; Tonn JC; Low MJ; Arzt E; Stalla GK; Paez-Pereda M. 2003. Laminin inhibits lactotroph proliferation and is reduced in early prolactinoma development. Mol Cell Endocrinol 207(1-2):13-20. [PubMed: 12972179]  [MGI Ref ID J:126844]

Li XX; Bek M; Asico LD; Yang Z; Grandy DK; Goldstein DS; Rubinstein M; Eisner GM; Jose PA. 2001. Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice. Hypertension 38(3):303-8. [PubMed: 11566895]  [MGI Ref ID J:103181]

Murer MG; Dziewczapolski G; Salin P; Vila M; Tseng KY; Ruberg M; Rubinstein M; Kelly MA; Grandy DK; Low MJ; Hirsch E; Raisman-Vozari R; Gershanik O. 2000. The indirect basal ganglia pathway in dopamine D(2) receptor-deficient mice. Neuroscience 99(4):643-50. [PubMed: 10974427]  [MGI Ref ID J:119592]

Narayanan S; Lam H; Christian L; Levine MS; Grandy D; Rubinstein M; Maidment NT. 2004. Endogenous opioids mediate basal hedonic tone independent of dopamine D-1 or D-2 receptor activation. Neuroscience 124(1):241-6. [PubMed: 14960355]  [MGI Ref ID J:90516]

Palmer AA; Low MJ; Grandy DK; Phillips TJ. 2003. Effects of a Drd2 deletion mutation on ethanol-induced locomotor stimulation and sensitization suggest a role for epistasis. Behav Genet 33(3):311-24. [PubMed: 12837020]  [MGI Ref ID J:103087]

Phillips TJ; Brown KJ; Burkhart-Kasch S; Wenger CD; Kelly MA; Rubinstein M; Grandy DK; Low MJ. 1998. Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors. Nat Neurosci 1(7):610-5. [PubMed: 10196569]  [MGI Ref ID J:50787]

Ralph RJ; Varty GB; Kelly MA; Wang YM; Caron MG; Rubinstein M ; Grandy DK ; Low MJ ; Geyer MA. 1999. The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice. J Neurosci 19(11):4627-33. [PubMed: 10341260]  [MGI Ref ID J:55027]

Ralph-Williams RJ; Lehmann-Masten V; Otero-Corchon V; Low MJ; Geyer MA. 2002. Differential effects of direct and indirect dopamine agonists on prepulse inhibition: a study in D1 and D2 receptor knock-out mice. J Neurosci 22(21):9604-11. [PubMed: 12417685]  [MGI Ref ID J:111572]

Risinger FO; Freeman PA; Rubinstein M; Low MJ; Grandy DK. 2000. Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice. Psychopharmacology (Berl) 152(3):343-50. [PubMed: 11105945]  [MGI Ref ID J:103899]

Schuff KG; Hentges ST; Kelly MA; Binart N; Kelly PA; Iuvone PM; Asa SL; Low MJ. 2002. Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. J Clin Invest 110(7):973-81. [PubMed: 12370275]  [MGI Ref ID J:79683]

Tang K; Low MJ; Grandy DK; Lovinger DM. 2001. Dopamine-dependent synaptic plasticity in striatum during in vivo development. Proc Natl Acad Sci U S A 98(3):1255-60. [PubMed: 11158626]  [MGI Ref ID J:127071]

Tillerson JL; Caudle WM; Parent JM; Gong C; Schallert T; Miller GW. 2006. Olfactory discrimination deficits in mice lacking the dopamine transporter or the D2 dopamine receptor. Behav Brain Res 172(1):97-105. [PubMed: 16765459]  [MGI Ref ID J:110704]

Tseng KY; Roubert C; Do L; Rubinstein M; Kelly MA; Grandy DK; Low MJ; Gershanik OS; Murer MG; Giros B; Raisman-Vozari R. 2000. Selective increase of Nurr1 mRNA expression in mesencephalic dopaminergic neurons of D2 dopamine receptor-deficient mice Brain Res Mol Brain Res 80(1):1-6. [PubMed: 11039723]  [MGI Ref ID J:64369]

Vinkers CH; Risbrough VB; Geyer MA; Caldwell S; Low MJ; Hauger RL. 2007. Role of dopamine D1 and D2 receptors in CRF-induced disruption of sensorimotor gating. Pharmacol Biochem Behav 86(3):550-8. [PubMed: 17324452]  [MGI Ref ID J:124479]

Wang H; Liang S; Burgdorf J; Wess J; Yeomans J. 2008. Ultrasonic vocalizations induced by sex and amphetamine in M2, M4, M5 muscarinic and D2 dopamine receptor knockout mice. PLoS ONE 3(4):e1893. [PubMed: 18382674]  [MGI Ref ID J:134260]

Zahniser NR; Simosky JK; Mayfield RD; Negri CA; Hanania T; Larson GA; Kelly MA; Grandy DK; Rubinstein M; Low MJ; Fredholm BB. 2000. Functional uncoupling of adenosine A(2A) receptors and reduced responseto caffeine in mice lacking dopamine D2 receptors. J Neurosci 20(16):5949-57. [PubMed: 10934242]  [MGI Ref ID J:112280]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
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.

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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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Fax: 207.288.6150
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phone:	207-288-6470
fax:	207-288-6655

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“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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