GENETICS OF NERVOUS SYSTEM DISEASESEvidence for resistance to MPTP in C57BL/6 × BALA/c F1 hybrids as compared with their progenitor strainsSedelis, Marco1,5; Hofele, Katja1; Auburger, Georg W.1,2; Morgan, Sarah1; Huston, Joseph P.1; Schwarting, Rainer K. W.3Author Information 1Institute of Physiological Psychology I and Center for Biological and Medical Research, Universitätsstrasse 1, 40225 Düsseldorf, Germany 2Department of Neurology, Heinrich-Heine-University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany 3NHGRI/NIH, 49 Convent Drive, Bethesda, MD 20892, USA 4General and Physiological Psychology, Philipps-University of Marburg, Biegenstrasse 12, 35032 Marburg, Germany 5Corresponding Author: Marco Sedelis, e-mail: email@example.com Acknowledgements: M.S. is a fellow of the Deutsche Forschungsgemeinschaft (DFG) doctoral program ‘Pathologische Prozesse des Nervensystems: Vom Gen zum Verhalten’. G.W.A. is a Heisenberg-fellow of the DFG. Received 5 January 2000; accepted 28 January 2000 NeuroReport: April 7, 2000 - Volume 11 - Issue 5 - p 1093-1096 Buy Abstract The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is capable of producing a syndrome in mice which shares major characteristics with human Parkinson's disease. There is evidence for a genetic influence on the degree of damage exerted by MPTP, since different strains of mice can dramatically differ in their response to MPTP. We produced reciprocal F1 hybrids by crossbreeding the MPTP-susceptible C57BL/6 strain with resistant BALB/c. These hybrids were compared to the parental strains using neural and behavioral measures in order to characterize the genetic transmission of MPTP-susceptibility. The F1 generation as a whole had a lower depletion of neostriatal dopamine levels than even found in BALB/c. Furthermore, there was no significant loss of tyrosine hydroxylase-positive cells in the substantia nigra and quick recovery from deficits in motor behavior in F1, herein resembling BALB/c. We suggest that several loci are involved in susceptibility to MPTP, and that the trait is under control of recessive susceptibility and/or dominant resistance alleles, which interact in F1, leading to extremely low susceptibility. © 2000 Lippincott Williams & Wilkins, Inc.