PINK1 mice

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PTEN-induced putative kinase 1 (PINK1) is a serine/threonine kinase that is localized to the mitochondria and implicated in autosomal recessive Parkinson’s disease. Multiple studies have shown that PINK1 mutations cause neurodegeneration and Parkinson’s like phenotypes in both cells and animal models. The PINK1flx/flx mouse line is important for studying parkinsons disease in a complex in vivo model.
The PINK1flx/flx mouse line was designed to employ the cre-lox system. PINK1 is located on chromosome 4 in Mus musculus. Exons 4 and 5 are flanked by loxP sites (primers below). Upon the introduction of cre recombinase (either by an injected virus or by genetic crossing to another transgenic mouse) the loxP sites will recombine and excise the flanked region of the gene. This allows us to create a mouse that does not express PINK1. We are able to do this on the germ line level, so the mouse never expresses PINK1. Or we can do this in a conditional manner, where we control the expression of PINK1 spatially, temporally, or both.
We can control the expression of PINK1 spatially by directly injecting AAV-Cre into a specific region of the brain. This causes the recombination of the loxP sites in that specific area only. We can temporally control the expression of PINK1 by crossing PINK1flx/flx mice with a tamoxifen inducible creER mouse line. Mice positive for both floxed PINK1 and the creER are allowed to age to a certain time point at which they will be injected with Tamoxifen. The tamoxifen will activate the creER and the floxed PINK1 will recombine.

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Christine Joseph
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