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

Kristin Hamre, Ruby Tharp, Kenneth Poon, Xiaoping Xiong, Richard J. Smeyne

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used as a potent 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 neuron 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 trait was dominant, additive or recessive, we crossed C57B1/6J mice with either SWR/J or AKR/J mice and examined the effect of MPTP on F1 C57BL/6J X SWR/J or F1 C57BL/6J X AKR/J animals. We find that all of the F1 animals were phenotypically identical to the C57BL/6J animals. In addition, no gender differences were noted in any of the MPTP-treated inbred mice or in the F1 animals. These results suggest that susceptibility to cell loss following MPTP is autosomal dominant and this polymorphism is carried on the C57BL/6J allele.

Original languageEnglish (US)
Pages (from-to)91-103
Number of pages13
JournalBrain Research
Volume828
Issue number1-2
DOIs
StatePublished - May 15 1999
Externally publishedYes

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Inbred AKR Mouse
Neurotoxins
Inbred C57BL Mouse
Parkinson Disease
Alleles
Pathology
Neurons
Injections

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

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. / Hamre, Kristin; Tharp, Ruby; Poon, Kenneth; Xiong, Xiaoping; Smeyne, Richard J.

In: Brain Research, Vol. 828, No. 1-2, 15.05.1999, p. 91-103.

Research output: Contribution to journalArticle

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