title: Animal models of Parkinson's disease: vertebrate genetics.
abstract: Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially mice, have aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of showing a broad range of phenotypes and, coupled with their conserved genetic and anatomical structures, provide unparalleled molecular and pathological tools to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. Here, we provide an overview of the generation and characterization of transgenic and knockout mice used to study PD followed by a review of the molecular insights that have been gleaned from current PD mouse models. Finally, potential approaches to refine and improve current models are discussed.
authors.affiliation: NeuroRegeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Yunjong
authors.initials: Y
authors.lastname: Lee
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D000882:Haplorhini; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000821:virology; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human