Parkin-deficient mice are not a robust model of parkinsonism

Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2174-9. doi: 10.1073/pnas.0409598102. Epub 2005 Jan 31.

Abstract

Mutations in the human parkin gene cause autosomal recessive juvenile parkinsonism, a heritable form of Parkinson's disease (PD). To determine whether mutations in the mouse parkin gene (Park2) also result in a parkinsonian phenotype, we generated mice with a targeted deletion of parkin exon 2. Using an extensive behavioral screen, we evaluated neurological function, motor ability, emotionality, learning, and memory in aged Parkin-deficient mice. The behavioral profile of Parkin-deficient mice on a B6;129S4 genetic background was strikingly similar to that of control mice, and most differences were not reproducible by using coisogenic mice on a 129S4 genetic background. Moreover, catecholamine levels in the striatum, olfactory bulb, and spinal cord of Parkin-deficient mice were normal. In contrast to previous studies using independently generated Parkin-deficient mice, we found no evidence for nigrostriatal, cognitive, or noradrenergic dysfunction. Understanding why Parkin-deficient mice do not exhibit robust signs of parkinsonism could advance knowledge and treatment of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamines / pharmacology
  • Animals
  • Behavior, Animal / physiology
  • Disease Models, Animal*
  • Emotions
  • Genotype
  • Humans
  • Learning
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nerve Tissue / chemistry
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / physiopathology
  • Phenotype
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Amphetamines
  • Ubiquitin-Protein Ligases
  • parkin protein