Differential strain susceptibility following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration acts in an autosomal dominant fashion: quantitative analysis in seven strains of Mus musculus

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used as a pote nt neurotoxin to approximate, in animals, the pathology that is observed in human Parkinson's disease. In this study, we examine the toxicity of MPTP in seven strains of mice, spanning a genetic continuum of Mus musculus as a prelude to uncovering complex traits associated with MPTP toxicity. Seven days following injection of 80 mg/kg MPTP (4 x 20 mg/kg every 2 h), we find that the individual mouse strains exhibit dramatic differences in SNpc neu ron survival, ranging from 63% cell loss in C57BL/6J mice to 14% cell loss in Swiss-Webster (SW) mice. In order to determine if the susceptibility tra it was dominant, additive or recessive, we crossed C57B1/6J mice with eithe r SWR/J or AKR/J mice and examined the effect of MPTP on Fl C57BL/6J x SWR/ J or Fl C57BL/6J x AKR/J animals. We find that all of the Fl animals were p henotypically identical to the C57BL/6J animals. In addition, no gender dif ferences were noted in any of the MPTP-treated inbred mice or in the Fl ani mals. These results suggest that susceptibility to cell loss following MPTP is autosomal dominant and this polymorphism is carried on the C57BL/6J all ele. (C) 1999 Elsevier Science B.V. All rights reserved.