Genetic Models Of Parkinsons Disease

In addition to pharmacological and neurotoxicant models of PD, which can be induced in a variety of different species, there are also rodent models derived from either spontaneous or directed genetic manipulation. Spontaneous rodent models of movement disorders, such as the founder mutations seen in the weaver mouse and AS/AGU rat, tend to arise fortuitously and depend on their recognition by researchers, followed by successful breeding. Another approach for establishing genetic rodent models is through targeting specific genes of interest creating a trans-genic mouse line. The recent identification of genes implicated in the etiology of familial forms of PD, including alpha-synuclein (PARK1), parkin (PARK2), UCH-L1 (PARK5), PINK1 (PARK6), DJ-1 (PARK7), and LRRK2 (PARK8), have provided a starting point in the development of specific transgenic mouse lines. The goal of these transgenic lines is to replicate in the rodent some of the neurochemical, pathological, or behavioral features of the human condition. This is not a simple matter, as illustrated by the wide range of outcomes in the characterization of alpha-synuclein transgenic lines. The findings from generating transgenic models targeting alpha-synuclein emphasize the complexity and variability in outcome measures with this approach. Although many different laboratories have generated alpha-synuclein transgenic mice, the importance of transgene sequence (wildtype or different mutant alleles), promoter strength and cell-type specificity, copy number, insertion site, and background strain all influence features of this model. The following sections will highlight both spontaneous and transgenic rodent models of PD, many of which are still in their early stages of development and characterization.

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