Animal models of Parkinson's disease: vertebrate genetics

Cold Spring Harb Perspect Med. 2012 Oct 1;2(10):a009324. doi: 10.1101/cshperspect.a009324.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal*
  • Haplorhini
  • Intracellular Signaling Peptides and Proteins / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mice
  • Mice, Knockout
  • Models, Genetic
  • Oncogene Proteins / genetics
  • Parkinson Disease / genetics*
  • Parkinson Disease / virology
  • Protein Deglycase DJ-1
  • Protein Kinases / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Rats
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • PTEN-induced putative kinase
  • Protein Serine-Threonine Kinases
  • PARK7 protein, human
  • Protein Deglycase DJ-1