Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease

Nat Neurosci. 2009 Jul;12(7):826-8. doi: 10.1038/nn.2349. Epub 2009 Jun 7.

Abstract

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. We created a LRRK2 transgenic mouse model that recapitulates cardinal features of the disease: an age-dependent and levodopa-responsive slowness of movement associated with diminished dopamine release and axonal pathology of nigrostriatal dopaminergic projection. These mice provide a valid model of Parkinson's disease and are a resource for the investigation of pathogenesis and therapeutics.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Antiparkinson Agents / therapeutic use
  • Apomorphine / therapeutic use
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Chromosomes, Artificial, Bacterial
  • Disease Models, Animal*
  • Dopamine / metabolism
  • Dopamine Uptake Inhibitors / pharmacology
  • Gene Transfer Techniques
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Levodopa / therapeutic use
  • Mice
  • Mice, Transgenic*
  • Movement Disorders / drug therapy
  • Movement Disorders / genetics
  • Mutation, Missense
  • Neurons / pathology
  • Neurons / physiology
  • Nomifensine / pharmacology
  • Parkinson Disease* / genetics
  • Parkinson Disease* / pathology
  • Parkinson Disease* / physiopathology
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism

Substances

  • Antiparkinson Agents
  • Dopamine Uptake Inhibitors
  • Nomifensine
  • Levodopa
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein-Serine-Threonine Kinases
  • Apomorphine
  • Dopamine