International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E38 The MPTP Mouse Model as Tool for Revealing the Genetics of Parkinson's Disease

K. Hofele1, M. Sedelis2, S. Morgan2, P. Kutz1, J. P. Huston2, R. K. W. Schwarting2, G. W. Auburger1. 1Dept. Neurology, 2Inst. Physiol. Psychol., Univ. of Dusseldorf, Germany

The neurotoxin MPTP is known to produce an experimental model of Parkinson's disease (PD) replicating most of the clinical features as well as the main biochemical and pathologic hallmarks of the disease. Previous studies have shown that inbred mouse strains can differ remarkably in their susceptibility to MPTP, thus indicating a strong genetic influence. Here, we present an experimental design to approach the genetics of PD using the MPTP mouse model. In the first step, the inbred strains C57BL/6 and Balb/c were characterized with respect to their behavioral and neural susceptibility to systemic treatment with MPTP. One critical aim opf this approach was to determine a neurotoxic dose which can be used in both sexes and strains. Our data show that C57BL/6 mice are more susceptible to MPTP-toxicity than Balb/c mice. Effects were found on the behavioral level as well as with respect to loss of neostriatal dopamine and cell loss in the substantia nigra. In the next and intermediate step, C57BL/6 and Balb/c mice were intercrossed to produce an F1 generation which was analyzed in the same way as the parental strains. In these animals a reduced behavioral and neurochemical vulnerability to MPTP treatment was found. Finally, an F2 generation was established which was treated with MPTP like the parental and F1 animals. Our data show the relationship between the behavioral and neurochemical outcome of toxin treatment in these animals. Studying the genetic variables which are apparently critical in the mouse model may be helpful to further determine the possible genetic background in PD.

Acknowledgements: M.S. and K.H. are fellows of the DFG graduate program "Pathological processes of the nervous system: from gene to behavior".


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