Strain Name:

B6.Cg-Tg(Pnkd*A7V*A9V,-DsRed)704Ljp/J

Stock Number:

022146

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This transgenic strain, mut Tg Pknd line 704, expresses an estimated 2 copies of the long isoform of the paroxysmal nonkinesigenic dyskinesia (Pnkd) gene mutated to include the A7V and A9V substitutions found in human PNKD patients. Following i.p. administration of ethanol or caffeine, mice exhibit nigrostriatal neurotransmission deficits and dyskinesia.

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

Former Names B6.Cg-Tg(Pnkd*A7V*A9V)704Ljp/J    (Changed: 26-APR-13 )
Type Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Louis Ptacek,   University of California, San Francisco

Description
The autosomal dominant episodic movement disorder, paroxysmal nonkinesigenic dyskinesia (PKND), is associated with two valine to alanine substitutions in the uncharacterized human gene, PNKD. This transgenic strain, mut Tg (line 704), expresses the long isoform of the Pnkd gene and the A7V and A9V substitutions. The long isoform of PNKD is expressed only in the central nervous system. In humans, PNKD movement disorder is observed following stress, caffeine or alcohol intake. Mice carrying the transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Following i.p. administration of ethanol or caffeine, transgenic mice exhibit nigrostriatal neurotransmission deficits, reduced extracellular dopamine levels in the striatum, an increased percentage of striatal dopamine release, and dyskinesia characterized by severe axial stiffness and abnormal limb movements. Non-induced mice exhibit lower glutathione levels in the frontal cortex. This mutant mouse strain may be useful in studies of autosomal dominant episodic movement disorder (PKND) and cellular redox regulation. No discernible phenotypic differences have been observed between transgenic line 671 (see Stock No. 018410) which carries an estimated single copy of the transgene and line 704 which carries approximately 2 copies. A DsRed insertion is believed to be non-functional.

Development
The bacterial artificial chromosome (BAC) RP24-112K19 containing the entire paroxysmal nonkinesiogenic dyskinesia (Pnkd) gene and 62 Kb of flanking sequence 5' to the AATG start site was altered to insert the mutations associated with human PNKD - valine to alanine substitutions at amino acid positions 7 (A7V) and 9 (A9V). An internal ribosomal entry site (IRES) followed by an enhanced red fluorescent protein (DsRED) also was inserted into the 3' UTR of Pnkd. This modified BAC was microinjected into the pronucleus of C57BL/6XSJL F1 oocytes. Founder mice (line 704) were established and found to have an estimated 2 copies of the transgene. These mut-Tg Pnkd transgenic mice were subsequently backcrossed to C57BL/6J for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony. The DsRED insertion is believed to be non-functional.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Pnkd
018409   B6.129-Pnkdtm1Ljp/J
018410   B6.Cg-Tg(Pnkd*A7V*A9V,-DsRed)671Ljp/J
022147   B6.Cg-Tg(Pnkd,-DsRed)445Ljp/J
View Strains carrying other alleles of Pnkd     (3 strains)

Strains carrying other alleles of RFP
006067   129-Gt(ROSA)26Sortm2(CAG-Dsred2/EGFP)Luo/J
006041   129-Gt(ROSA)26Sortm3(CAG-EGFP/Dsred2)Luo/J
012687   B6(129S4)-Tg(SYN1-icre/mRFP1)9934Rdav/J
017456   B6(C)-Tg(CAG-mCherry,-GAL4)769Gsn/J
017457   B6(C)-Tg(CAG-mCherry,-GAL4)774Gsn/J
017614   B6(Cg)-Tyrc-2J Tg(UBC-mCherry)1Phbs/J
021011   B6(D2)-Tg(CAG-Brainbow1.0)2Eggn/J
021012   B6(D2)-Tg(CAG-Brainbow1.0)3Eggn/J
007676   B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J
006080   B6.129-Gt(ROSA)26Sortm2(CAG-Dsred2/EGFP)Luo/J
006075   B6.129-Gt(ROSA)26Sortm3(CAG-EGFP/Dsred2)Luo/J
007914   B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J
007909   B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J
017863   B6.Cg-Tg(Adora2a-Chrm3*,-mCherry)AD6Blr/J
005884   B6.Cg-Tg(CAG-mRFP1)1F1Hadj/J
025525   B6.Cg-Tg(Cx3cl1/mCherry)1Jung/J
016204   B6.Cg-Tg(Drd1a-tdTomato)6Calak/J
018410   B6.Cg-Tg(Pnkd*A7V*A9V,-DsRed)671Ljp/J
022147   B6.Cg-Tg(Pnkd,-DsRed)445Ljp/J
007901   B6.Cg-Tg(Thy1-Brainbow1.0)HLich/J
007911   B6.Cg-Tg(Thy1-Brainbow1.1)MLich/J
007921   B6.Cg-Tg(Thy1-Brainbow2.1)RLich/J
010984   B6;129P-Upk1btm1Pzg/J
013139   B6;129P2-Ifitm3tm1(RFP)Pzg/J
006720   B6;129P2-Olfr124tm4Mom/MomJ
010983   B6;129S-Id3tm1Pzg/J
010986   B6;129S-Osr2tm1Pzg/J
018128   B6;129S-Tg(Prox1-tdTomato)12Nrud/J
007908   B6;129S6-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J
007905   B6;129S6-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J
017954   B6;C-Tg(CAG-Epha4/Efna5,-mCherry)1Slp/J
018936   B6;C-Tg(Erv4-tdTomato)449Slp/J
007984   B6;CBA-Tg(H/Olfr16-taumCherry,-tauGFP)11Mom/MomJ
007985   B6;CBA-Tg(H/Olfr16-taumCherry,-tauGFP)13Mom/MomJ
007982   B6;CBA-Tg(H/Olfr16-taumRFP,-tauGFP)8Mom/MomJ
007983   B6;CBA-Tg(H/Olfr16-taumRFP,-tauGFP)9Mom/MomJ
007910   B6;CBA-Tg(Thy1-Brainbow1.0)LLich/J
017496   B6;D-Tg(Lfng-TagRFP/cre/ERT2)8Amc/J
018682   B6;D-Tg(Meox1-TagRFP/cre/ERT2)30Amc/J
018683   B6;D-Tg(Wnt11-TagRFP/cre/ERT2)28Amc/J
013137   B6;D2-Tg(Akr1b7-RFP)9Amc/J
021577   B6;D2-Tg(Myh6*-mCherry)2Mik/J
015853   B6;DBA-Tg(Cited1-TagRFP)26Amc/J
008374   C57BL/6-Foxp3tm1Flv/J
024046   C57BL/6-Tg(Csf1r-HBEGF/mCherry)1Mnz/J
022766   C57BL/6-Tg(Prox1-tdTomato)12Nrud/J
021119   C57BL/6J-Tg(Dlx2-cre,-mCherry)4Grsr/GrsrJ
021423   C57BL/6J-Tg(Dlx2-cre,-mCherry)9Grsr/GrsrJ
018754   C57BL/6J-Tg(Tbx22,-cre,-mCherry)1Grsr/GrsrJ
018542   FVB-Tg(Kdr-mCherry)1Medi/J
021853   FVB-Tg(Myh6-mCherry/Map1lc3a)1Rag/J
018067   FVB-Tg(Prism)1849Htz/J
018071   FVB-Tg(Prism)1861Htz/J
018068   FVB-Tg(Prism)1989Htz/J
007576   STOCK Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J
017530   STOCK Igs2tm2(ACTB-tdTomato,-EGFP)Luo Trp53tm1Tyj Nf1tm1Par/J
013749   STOCK Iis2tm1(ACTB-EGFP,-tdTomato)Luo/J
013751   STOCK Iis2tm2(ACTB-tdTomato,-EGFP)Luo/J
017923   STOCK Iis3tm2.1(ACTB-EGFP*,-tdTomato)Luo/J
017472   STOCK Tg(Acp5-CFP,Ibsp-YFP,Dmp1-RFP)1Pmay/J
014177   STOCK Tg(Afp-mCherry)1Hadj/J
017919   STOCK Tg(CAG-EGFP,-dsRed2/RNAi:Tardbp)6Zxu/J
013753   STOCK Tg(CAG-KikGR)33Hadj/J
013754   STOCK Tg(CAG-KikGR)75Hadj/J
017934   STOCK Tg(CAG-dsRed2/RNAi:Tardbp)6Zxu/J
005645   STOCK Tg(CAG-mRFP1)1F1Hadj/J
017465   STOCK Tg(Col10a1-mCherry)3Pmay/J
016921   STOCK Tg(Myh2-DsRed2)1Jrs/J
024850   STOCK Tg(Sp7/mCherry)2Pmay/J
021226   STOCK Tg(Thy1-Brainbow3.1)18Jrs/J
021225   STOCK Tg(Thy1-Brainbow3.1)3Jrs/J
021227   STOCK Tg(Thy1-Brainbow3.2)7Jrs/J
017470   STOCK Tg(Tnc-mCherry)2Pmay/J
011108   STOCK Tg(Ttr-RFP)1Hadj/J
016981   STOCK Tg(Uchl1-HIST2H2BE/mCherry/EGFP*)FSout/J
017906   STOCK Tg(tetO-hop/EGFP,-COP4/mCherry)6Kftnk/J
View Strains carrying other alleles of RFP     (76 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Paroxysmal Nonkinesigenic Dyskinesia 1; PNKD1
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tg(Pnkd*A7V*A9V,-DsRed)704Ljp/0

        B6.Cg-Tg(Pnkd*A7V*A9V,-DsRed)704Ljp
  • behavior/neurological phenotype
  • abnormal behavioral response to xenobiotic
    • mice challenged with an injection of caffeine exhibit dyskinetic attacks about 10-15 minutes after treatment that persists for 2 hours compared to moderate hyperlocomotion during the first hour in wild-type controls   (MGI Ref ID J:192798)
    • mice challenged with an injection of ethanol exhibit dyskinetic attacks beginning 10 minutes after injection and lasting 2-4 hours, and show severe axial stiffness, with some abnormal movements of the limbs   (MGI Ref ID J:192798)
  • abnormal motor capabilities/coordination/movement
    • mice exhibit dyskinesia after stress such as prolonged handling, that includes oral-facial movements such as tongue protrusions and stereotypic movements such as repetitive sniffing and rearing in one location   (MGI Ref ID J:192798)
  • homeostasis/metabolism phenotype
  • abnormal dopamine level
    • while dopamine levels in the striatum are normal at rest, after injection of caffeine, mutants exhibit higher levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), higher DOPAC/dopamine ratios, and higher levels of the terminal metabolite of dopamine, homovanillic acid, than wild-type mice   (MGI Ref ID J:192798)
    • however, mutants exhibit normal levels of serotonin and its metabolized product following stimulation with caffeine   (MGI Ref ID J:192798)
    • decreased dopamine level
      • extracellular concentration of dopamine is less than 40% of that of controls under basal conditions, indicating lower striatal dopamine release at rest   (MGI Ref ID J:192798)
  • nervous system phenotype
  • abnormal dopamine level
    • while dopamine levels in the striatum are normal at rest, after injection of caffeine, mutants exhibit higher levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), higher DOPAC/dopamine ratios, and higher levels of the terminal metabolite of dopamine, homovanillic acid, than wild-type mice   (MGI Ref ID J:192798)
    • however, mutants exhibit normal levels of serotonin and its metabolized product following stimulation with caffeine   (MGI Ref ID J:192798)
    • decreased dopamine level
      • extracellular concentration of dopamine is less than 40% of that of controls under basal conditions, indicating lower striatal dopamine release at rest   (MGI Ref ID J:192798)
  • abnormal synaptic transmission
    • mutants exhibit deficits in nigrostriatal neurotransmission characterized by low levels of dopamine release, enhanced dopamine reuptake, and increase of dopamine release in response to caffeine and ethanol   (MGI Ref ID J:192798)
    • abnormal synaptic dopamine release
      • mutants exhibit lower striatal dopamine release at rest, but an increase in percentage of striatal dopamine release in response to challenges with caffeine or stress   (MGI Ref ID J:192798)
View Research Applications

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

Metabolism Research

Neurobiology Research
Ataxia (Movement) Defects
Metabolic Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Pnkd*A7V*A9V,-DsRed)704Ljp
Allele Name transgene insertion 704, Louis J Ptacek
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) Tg(Pnkd*A7V*A9V)704Ljp;
Strain of Origin(C57BL/6 x SJL)F1
Expressed Gene RFP, Red Fluorescent Protein, coral
Red Fluorescent Protein (RFP), derived from marine invertebrate organisms such as the soft coral Discosoma spp and reef coral, Heteractis crispa, is a versatile reporter molecule which has found use in many biological applications. The wild type protein, which is an obligate tetramer, is not well tolerated in mammalian systems. The original molecule has been modified in order to optimize expression to mammalian physiology (examples include monomeric RFP, mRFP1, DsRed, etc).
Promoter Pnkd, paroxysmal nonkinesiogenic dyskinesia, mouse, laboratory
Molecular Note The transgene contains a BAC with the nucleotide substitutions that lead to the amino acid substitutions of valine for alanine at positions 7 and 9. An IRES/DsRed was inserted into the 3'UTR. This transgene is predicted to produce only the long isoform. Lines 671, 676, and 704 were generated. [MGI Ref ID J:172066] [MGI Ref ID J:192798]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Pnkd,-DsRed)445Ljp, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Shen Y; Lee HY; Rawson J; Ojha S; Babbitt P; Fu YH; Ptacek LJ. 2011. Mutations in PNKD causing paroxysmal dyskinesia alters protein cleavage and stability. Hum Mol Genet 20(12):2322-32. [PubMed: 21487022]  [MGI Ref ID J:172066]

Additional References

Tg(Pnkd*A7V*A9V,-DsRed)704Ljp related

Lee HY; Nakayama J; Xu Y; Fan X; Karouani M; Shen Y; Pothos EN; Hess EJ; Fu YH; Edwards RH; Ptacek LJ. 2012. Dopamine dysregulation in a mouse model of paroxysmal nonkinesigenic dyskinesia. J Clin Invest 122(2):507-18. [PubMed: 22214848]  [MGI Ref ID J:192798]

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, G200.

Colony Maintenance

Breeding & HusbandryWhile maintaining a live colony, these mice are bred as hemizygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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