Parkinson's disease: genetic versus toxin-induced rodent models.
Parkinson's disease (PD), a common progressive neurodegenerative disorder, is characterized by degeneration of dopamine neurons in the substantia nigra and neuronal proteinaceous aggregates called Lewy bodies (LBs). The etiology of PD is probably a combination of environmental and genetic factors. Recent progress in molecular genetics has identified several genes causing PD, including alpha-synuclein, leucine-rich repeat kinase 2 (LRRK2), Parkin, DJ-1 and PTEN-induced kinase 1 (PINK1), many of them coding for proteins found in LBs and/or implicated in mitochondrial function. However, the mechanism(s) leading to the development of the disease have not been identified, despite intensive research. Animal models help us to obtain insights into the mechanisms of several symptoms of PD, allowing us to investigate new therapeutic strategies and, in addition, provide an indispensable tool for basic research. As PD does not arise spontaneously in animals, characteristic and specific functional changes have to be induced by administration of toxins or by genetic manipulations. This review will focus on the comparison of three types of rodent animal models used to study different aspects of PD: (a) animal models using neurotoxins; (b) genetically modified mouse models reproducing findings from PD linkage studies or based on ablation of genes necessary for the development and survival of dopamine neurons; and (c) tissue-specific knockouts in mice targeting dopamine neurons. The advantages and disadvantages of these models are discussed.
Terzioglu
Mügen
M
 Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Galter
Dagmar
D
 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D009498:Neurotoxins / Q000633:toxicity*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D013238:Stereotaxic Techniques
D009498:Neurotoxins