BACKGROUND:  Existing genetic mouse models based on known Parkinson's disease mutations recapitulate aspects of dopaminergic (DA) neuron dysfunction without exhibiting progressive degeneration of DA cell bodies. Furthermore, other genetic models, based on genes not linked to familial PD, do exhibit a DA neuron degeneration phenotype. However, in most cases, the loss of DA neurons occurs early in development, and its direct relevance to PD remains hypothetical.

INNOVATION:  UCLA scientists have developed a mouse model of Parkinson's disease with late onset behavioral and neuropathological phenotypes. This novel mammalian genetic model can be used to study the mechanisms underlying age-dependent and the slowly progressive form of DA neuron degeneration.

POTENTIAL APPLICATIONS 

• This mouse model can be use to perform in vivo preclinical testing of PD therapeutics

ADVANTAGES

• This model exhibits late-onset and progressive hypokinetic motor deficits
• Age-dependent DA neuron degeneration.
• Significant reduction of striatal dopamine level
• Age-dependent accumulation of proteinase K resistant alpha-synuclein in substantia nigra

DEVELOPMENT-TO-DATE:  Transgenic mouse model characterization has been completed.

Related Papers (Selected)

• Lu XH, Fleming SM, Meurers B, Ackerson LC, Mortazavi F, Lo V, Hernandez D, Sulzer D, Jackson GR, Maidment NT, Chesselet MF, Yang XW. Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein. J Neurosci. 29(7):1962-76 (2009). [more]

Reference: UCLA Case No. 2009-718