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 from 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.
Cook
Ruby
R
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA.
Lu
Lu
L
Gu
Jing
J
Williams
Robert W
RW
Smeyne
Richard Jay
RJ
D000818:Animals; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D040641:Quantitative Trait Loci / Q000187:drug effects* / Q000235:genetics*; D013045:Species Specificity; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology