Identification of a single QTL, Mptp1, for susceptibility to MPTP-induced substantia nigra pars compacta neuron loss in mice

The loss of substantia nigra pars compacta (SNpc) neurons seen in idiopathic Parkinson's disease is hypothesized to result fro. m, a genetic susceptibility to an unknown environmental toxin. MPTP has been used as a prototypical toxin, since exposure to this drug results in variable SNpc cell death in several vertebrate species, including man and mouse. Previously, we have shown that C57BL/6J mice are sensitive to this compound, while Swiss-Webster mice are resistant. In this study, we intercrossed these mouse strains to map quantitative trait loci (QTL) for MPTP sensitivity. Using genome wide PCR analysis, we found that a single major QTLs, Mptp1, located near the distal end of chromosome 1 between D1Mit113 and D1Mit293, accounts for the majority of the strain sensitivity to MPTP. (C) 2002 Elsevier Science B.V. All rights reserved.