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.
Louis Ptacek, University of California, San Francisco
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence) |
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.
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.
Expressed Gene | RFP, Red Fluorescent Protein, coral |
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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. |
Allele Name | transgene insertion 671, Louis J Ptacek |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | mut-Tg; Tg(Pnkd*A7V*A9V)671Ljp |
Gene Symbol and Name | Tg(Pnkd*A7V*A9V,-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 |
While maintaining a live colony, these mice are bred as hemizygotes.
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(Pnkd*A7V*A9V)671Ljp |
Frozen Mouse Embryo | B6.Cg-Tg(Pnkd*A7V*A9V -DsRed)671Ljp/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Tg(Pnkd*A7V*A9V -DsRed)671Ljp/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Tg(Pnkd*A7V*A9V -DsRed)671Ljp/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.Cg-Tg(Pnkd*A7V*A9V -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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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