Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter
Section snippets
Generation of null DJ-1 mice
Mice deficient in DJ-1 protein were generated with an embryonic stem cell line from a library created with a gene trap targeting vector (Baygenomics, Davis, CA). These ES cell lines were modified with the random insertion of vector containing an En2 intron–exon splice acceptor followed by the βgeo gene (a fusion of beta-galactosidase and neomycin resistance genes). The ES cell line (XE726) was determined by its 5′RACE sequence to have the βgeo trap insertion located in the DJ-1 gene locus in
DJ-1 −/− characterization
DJ-1-deficient mice were generated using an ES cell line (XE726) further modified with the random insertion of construct containing an En2 intron–exon splice acceptor followed by the βgeo gene (Fig. 1A). Immunohistochemical observation revealed lack of DJ-1 immunoreactivity in genotypic null mice. In contrast, wild-type mice showed robust DJ-1 staining throughout the brain (Figs. 1B, C). The protein was present within neurons as well as non-neuronal cells with morphological features of
Discussion
Here we characterized a new line of transgenic mice deficient in DJ-1. Behavioral, neurochemical and pathological findings in these animals are similar to those previously reported in other DJ-1 knockout mice (Chen et al., 2005, Goldberg et al., 2005, Kim et al., 2005). In particular, we observed a slight deficit in locomotor behavior, which was not accompanied by a reduction in striatal DA and DA metabolites or a decrease in DAergic cell number in the substantia nigra. An important original
Acknowledgments
The authors thank Dr. Jennifer Tillerson for the assistance with behavioral assays and Arjun Raman for the IT-related assistance. This work was funded by the Michael J. Fox Foundation (A.B.M.-B.) and the NIH (National Institute of Environmental Health Sciences, ES 012077, J.W.L., D.A.D., A.B.M.-B.; ES 01268, G.W.M.; National Institute of Mental Health, Intramural Research Program, C.R.G.).
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