These knock-in mice contain a mutation designed to replace gene function of the endogenous mouse Pink1 gene with the loss-of-function mutation, G309D, and a loxP-flanked neomycin resistance cassette (neo). These mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.
Georg Auburger, University Medical School
These mice contain a mutation designed to replace gene function of the endogenous mouse Pink1 gene with the loss-of-function mutation, G309D, and a loxP-flanked neomycin resistance cassette (neo). Mice homozygous for Pink1-/- are viable and fertile. Mice with this mutation carry the same loss-of-function mutation found in early-onset PARK6-linked Parkinson's disease (PD). Unlike other PD models, these mice lack peripheral paralysis, and exhibit normal motor performance, coordination, anxiety, and lifespan. They also lack lewy bodies and have reduced expression of α-synuclein mRNA. As these mice age they exhibit a progressive reduction of weight, a reduction of locomotor activity, and abnormal dopamine levels. These mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.
The targeting construct contains exon 5 of the mouse PTEN induced putative kinase 1 (Pink1) gene. Nucleotide 8343 in exon 5 was changed from a G to an A, reflecting the loss-of-function mutation, G309D, found in early-onset PARK6-linked Parkinson's Disease (PD). The targeting vector also contains a loxP-flanked neomycin resistance cassette (neo). This targeting construct, designed to replace exons 5 of the mouse Pink1 gene, was electroporated into 129/SvEv-derived embryonic stem (ES) cell line. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric mice were bred to C57BL/6 mice and the colony was maintained on a mixed B6;129 background. Upon arrival at The Jackson laboratory, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation.
|Allele Name||targeted mutation 1, Georg Auburger|
|Allele Type||Targeted (Null/Knockout, Humanized sequence)|
|Allele Synonym(s)||targeted mutation 1, Georg Auburger; Pink1tm1Aub|
|Gene Symbol and Name||Pink1, PTEN induced putative kinase 1|
|Gene Synonym(s)||RIKEN cDNA 1190006F07 gene; BRPK; 1190006F07Rik; expressed sequence AW557854; expressed sequence AU042772; AU042772; AW557854; PARK6; 1190006F07Rik; brpk|
|Promoter||Pink1, PTEN induced putative kinase 1, mouse, laboratory|
|Strain of Origin||129|
|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, homozygous mice may be bred together.
When using the Pink1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #013050 in your Materials and Methods section.
|Heterozygous for Pink1<tm1Aub>|
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.
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