From mouse models to human behavior: Testing candidate genes for alcoholism

C. Fehr; A. Tadic; L. G. Schmidt; T. Sander; K. Lenzen; P. Nuernberger; I. Anghelescu; A. Szegedi

doi:10.1055/s-2003-825324

Pharmacopsychiatry, Inhaltsverzeichnis

From mouse models to human behavior: Testing candidate genes for alcoholism

C Fehr ¹, A Tadic ¹, LG Schmidt ¹, T Sander ², K Lenzen ², P Nuernberger ², I Anghelescu ³, A Szegedi ³

¹Department of Psychiatry, University of Mainz, Germany
²Gene mapping center and Department of Molecular Genetics, Max Delbrück Center, Berlin
³Department of Psychiatry, Campus Benjamin Franklin, Free University of Berlin, Germany.

Abstract

Genetic studies in mouse inbred strain crosses have reported a detailed map of gene loci contributing to different ethanol-mediated traits such as ethanol withdrawal, ethanol locomotor activation and ethanol preference. Using high resolution mapping experiments, a quantitative trait locus (QTL) that accounted for 26% of the genetic variance in acute alcohol withdrawal severity (Alcw2) was mapped to 1.78 Mb of genomic sequence on the mid portion of mouse chromosome four (1). Sequencing of candidate genes within the QTL showed that the gene encoding the multiple PDZ domain protein (Mpdz) was highly polymorphic between the different animal strains.

Within the current study, we test for association between Mpdz and different alcoholism withdrawal and sensitivity phenotypes among human alcohol dependent patients and healthy controls. Comparisons on other likely candidate genes deriving from ongoing animal studies will be included.

1. Fehr, C. et al. J. Neuroscience 22 (2002) 3730–3738.