This double mutant strain expresses mutant human A53T alpha-synuclein (SNCA) and carries a targeted mutation for Pink1, PTEN induced putative kinase 1, and has applications in studies of the early stages of Parkinson's Disease.
Georg Auburger, University Medical School
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout, Humanized sequence) | Pink1 | PTEN induced putative kinase 1 |
These double mutant mice overexpress the mutant A53T human SNCA, synuclein, alpha (non A4 component of amyloid precursor), and are deficient in endogenous mouse Pink1, PTEN induced putative kinase 1. Mice that are homozygous for both the transgene and the Pink1tm1Aub allele develop a behavior phenotype at 3 months of age, consisting of impaired spontaneous locomotion in open field tests for horizontal and vertical activity. This behaviour deficit appears much later also in the single mutant mice. In addition, the brain transcriptome profile in striatum of homozygous double mutants shows many consistent early alterations in the pathways of trophic signaling to mitochondria and apoptosis, which are not apparent in the transcriptome profiles of single mutants.
For the Pink1tm1Aub targeted mutation strain, a targeting construct containing a nucleotide substitution from a G to an A at nucleotide 8343 in exon 5, a loxP-flanked NEO cassette, was electroporated into a unspecified 129/SvEv-derived embryonic stem (ES) cell line. Correctly targeted ES cells were injected into blastocysts. The colony was maintained on a 129/SvEv background.
For the Tg(Prnp-SNCA*A53T)AAub transgenic strain, a transgenic construct containing the entire translated portion of the mutant A53T human alpha-synuclein (SNCA) from position 22 to 515, driven by an ~3.5 kb fragment of the mouse prion protein promoter (Prnp), and polyadenylation signal sequence, was injected into fertilized FVB/N mouse eggs. Founder line A was subsequently established.
The strains were then intercrossed to generate double mutant mice that were heterozygous for the Pink1tm1Aub allele and Tg(Prnp-SNCA*A53T)AAub transgene. The double heterozygotes were then crossed to generate mice homozygous for both mutations. The mice were maintained on a mixed 129;FVB background. Upon arrival at The Jackson Laboratory, the mice were crossed to FVB/NJ (Stock No. 001800) at least once to establish the colony.
Expressed Gene | SNCA, synuclein alpha, human |
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Site of Expression | |
Site of Expression |
Allele Name | transgene insertion A, Georg Auburger |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | A53T; PrPmtA; PrPmtB; Tg(Prnp-SNCA*A53T)BAub |
Gene Symbol and Name | Tg(Prnp-SNCA*A53T)AAub, transgene insertion A, Georg Auburger |
Gene Synonym(s) | |
Promoter | Prnp, prion protein, mouse, laboratory |
Expressed Gene | SNCA, synuclein alpha, human |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | A construct containing the entire translated portion of human alpha-synuclein, SNCA from position 22 to 515, driven by an ~3.5 kb fragment of the mouse prion protein promoter, Prnp, was generated. The SNCA cDNA was followed by polyadenylation sequences derived from the 3' untranslated region of the boving growth hormone gene. This construct was microinjected into pronuclei of fertilized FVB/N ova.Transgenic protein expression was detected in the neuropil, with, more rarely, additional protein within neuronal cell bodies and neurites in the brain and motoneurons in the spinal cord. Two lines, A and B, were generated, have both been extensively studied, showing extremely similar phenotypes (J:86222, J:124976). |
Mutations Made By | Robert Nussbaum, University of California San Francisco |
Allele Name | targeted mutation 1, Georg Auburger |
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Allele Type | Targeted (Null/Knockout, Humanized sequence) |
Allele Synonym(s) | |
Gene Symbol and Name | Pink1, PTEN induced putative kinase 1 |
Gene Synonym(s) | |
Promoter | Pink1, PTEN induced putative kinase 1, mouse, laboratory |
Strain of Origin | 129 |
Chromosome | 4 |
Molecular Note | A p.G308D (g8343a) mutation was created in exon 4 and a floxed neo cassette in inverse orientation was inserted into intron 5 via homologous recombination. The mutation is the equivalent of the G309D mutation found in Parkinson's Disease patients. Northern blot and saturation RT-PCR of splice boundaries in brain and liver mRNA analysis confirmed the absence of full length transcript expression. Saturation RT-PCR also suggests the residual expression of low levels of a large mutant mRNA. |
Mutations Made By | Georg Auburger, University Medical School |
When maintaining a live colony, these mice can be bred as homozygotes for both the targeted mutation and the transgene.
When using the FVB;129-Pink1tm1Aub Tg(Prnp-SNCA*A53T)AAub/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017678 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous for Pink1<tm1Aub>, Hemizygous for Tg(Prnp-SNCA*A53T)AAub |
Frozen Mouse Embryo | FVB;129-Pink1<tm1Aub> Tg(Prnp-SNCA*A53T)AAub/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB;129-Pink1<tm1Aub> Tg(Prnp-SNCA*A53T)AAub/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB;129-Pink1<tm1Aub> Tg(Prnp-SNCA*A53T)AAub/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | FVB;129-Pink1<tm1Aub> Tg(Prnp-SNCA*A53T)AAub/J Frozen Embryo | $3373.50 |
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