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)|
|Gene Symbol and Name||Pink1, PTEN induced putative kinase 1|
|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.
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