Parkin-deficient mice are not a robust model of parkinsonism

FA Perez, RD Palmiter - Proceedings of the National …, 2005 - National Acad Sciences
FA Perez, RD Palmiter
Proceedings of the National Academy of Sciences, 2005National Acad Sciences
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 …
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.
National Acad Sciences