Genetic mouse models of parkinsonism: strengths and limitations.
Parkinson's disease (PD) is a progressive neurodegenerative disorder. Patients with PD display a combination of motor symptoms including resting tremor, rigidity, bradykinesia, and postural instability that worsen over time. These motor symptoms are related to the progressive loss of dopamine neurons in the substantia nigra pars compacta. PD patients also suffer from nonmotor symptoms that may precede the cardinal motor symptoms and that are likely related to pathology in other brain regions. Traditional toxin models of PD have focused on the nigrostriatal pathway and the loss of dopamine neurons in this region, and these models have been important in our understanding of PD and in the development of symptomatic treatments for the disease. However, they are limited in that they do not reproduce the full pathology and progression seen in PD, thus creating a need for better models. The recent discovery of specific genes causing familial forms of PD has contributed to the development of novel genetic mouse models of PD. This review discusses the validity, benefits, and limitations of these new models.
Fleming
Sheila M
SM
Departments of Neurology and Neurobiology, The David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA.
Fernagut
Pierre-Olivier
PO
Chesselet
Marie-Françoise
MF
D000818:Animals; D001035:Aphakia / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071617:Protein Deglycase DJ-1; D014157:Transcription Factors / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C539882:NR4A2 protein, human; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D015513:Oncogene Proteins; D014157:Transcription Factors; D051844:alpha-Synuclein; C433629:homeobox protein PITX3; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1