Overview

This transgenic strain, mut Tg Pknd line 671, expresses an estimated 1 copy 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.

Donating Investigator

Louis Ptacek, University of California, San Francisco

Genetic overview

Genetic Background	Generation

Tg(PnkdA7VA9V,-DsRed)671Ljp

Allele Type
Transgenic (Inserted expressed sequence)

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Research Applications

Neurobiology Research
Research Tools
Metabolism Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 671), 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 which carries an estimated single copy of the transgene and line 704 (see Stock No. 022146) which carries approximately 2 copies.

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 671) were established and found to have an estimated single copy of the transgene. The donating investigator reported that these mut-Tg Pnkd transgenic mice were subsequently backcrossed to C57BL/6J for at least 10 generations (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Expression Data

Expressed Gene	RFP, Red Fluorescent Protein, coral
Site of Expression	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.

Control Suggestions

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):2322-32PubMed: 21487022 MGI: J:172066

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Genetics

Tg(PnkdA7VA9V,-DsRed)671Ljp

Allele Symbol: Tg(PnkdA7VA9V,-DsRed)671Ljp

Allele Name	transgene insertion 671, Louis J Ptacek
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	transgene insertion 671, Louis J Ptacek; Tg(PnkdA7VA9V,-DsRed)671Ljp
Gene Symbol and Name	Tg(PnkdA7VA9V,-DsRed)671Ljp, transgene insertion 671, Louis J Ptacek
Gene Synonym(s)
Promoter	Pnkd, paroxysmal nonkinesiogenic dyskinesia, mouse, laboratory
Expressed Gene	RFP, Red Fluorescent Protein, coral
Site of Expression	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.
Strain of Origin	(C57BL/6 x SJL)F1
Chromosome	UN
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.
Mutations Made By	Louis Ptacek, University of California, San Francisco

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

paroxysmal nonkinesigenic dyskinesia 1

Research Areas By Genotype

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

Neurobiology Research
- Metabolic Defects
- Ataxia (Movement) Defects
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Fluorescent protein expression in neural tissue
Research Tools
- Fluorescent Proteins
Metabolism Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Tg(PnkdA7VA9V,-DsRed)671Ljp/0
B6.Cg-Tg(PnkdA7VA9V,-DsRed)671Ljp

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
- 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

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

homeostasis/metabolism phenotype

abnormal dopamine level
- Normal - however, mutants exhibit normal levels of serotonin and its metabolized product following stimulation with caffeine
- ite of dopamine, homovanillic acid, than wild-type mice
- 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

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

nervous system phenotype

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

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

References

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):2322-32PubMed: 21487022 MGI: J:172066

Additional - Tg(PnkdA7VA9V,-DsRed)671Ljp related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Generic DsRed
- Probe:Generic DsRed Probe
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as hemizygotes.
- Additional Breeding and Husbandry Support
Citation
When using the B6.Cg-Tg(Pnkd*A7V*A9V,-DsRed)671Ljp/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018410 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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(PnkdA7VA9V)671Ljp

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Tg(PnkdA7VA9V -DsRed)671Ljp/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.Cg-Tg(PnkdA7VA9V -DsRed)671Ljp/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.Cg-Tg(PnkdA7VA9V -DsRed)671Ljp/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.Cg-Tg(PnkdA7VA9V -DsRed)671Ljp/J Frozen Embryo	$3373.50

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Pnkd*A7V*A9V,-DsRed)671Ljp

Allele Symbol: Tg(Pnkd*A7V*A9V,-DsRed)671Ljp

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Pnkd*A7V*A9V,-DsRed)671Ljp/0B6.Cg-Tg(Pnkd*A7V*A9V,-DsRed)671Ljp

behavior/neurological phenotype

homeostasis/metabolism phenotype

nervous system phenotype

References

Additional - Tg(Pnkd*A7V*A9V,-DsRed)671Ljp related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tg(PnkdA7VA9V,-DsRed)671Ljp

Allele Symbol: Tg(PnkdA7VA9V,-DsRed)671Ljp

Genotype: Tg(PnkdA7VA9V,-DsRed)671Ljp/0
B6.Cg-Tg(PnkdA7VA9V,-DsRed)671Ljp

Additional - Tg(PnkdA7VA9V,-DsRed)671Ljp related