Parkin-deficient mice are not a robust model of parkinsonism

doi:10.1073/pnas.0409598102

Parkin-deficient mice are not a robust model of parkinsonism

Francisco A. Perez*,† and
Richard D. Palmiter*,‡,§

^*Graduate Program in Neurobiology and Behavior, ^†Medical Scientist Training Program, and ^‡Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195

Contributed by Richard D. Palmiter, December 21, 2004

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.

Footnotes

↵ § To whom correspondence should be addressed at: Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Health Sciences Building, Room J661D, Box 357370, Seattle, WA 98195. E-mail: palmiter{at}u.washington.edu.
Author contributions: F.A.P. and R.D.P. designed research; F.A.P. performed research; F.A.P. contributed new reagents/analytic tools; F.A.P. analyzed data; F.A.P. wrote the paper; and R.D.P. designed targeting strategy.
Abbreviations: PD, Parkinson's disease; AR-JP, autosomal recessive juvenile parkinsonism; B6, C57BL/6.
Data deposition: A description of the Park2^tm1Rpa allele has been deposited in the Mouse Genome Informatics database (accession no. 3055212).
Freely available online through the PNAS open access option.