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Pawlak, C.R.* ; Sanchis-Segura, C. ; Soewarto, D. ; Wagner, S. ; Hrabě de Angelis, M. ; Spanagel, R.*

A phenotype-driven ENU mutagenesis screen for the identification of dominant mutations involved in alcohol consumption.

Mamm. Genome 19, 77-84 (2008)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The aim of this study was the application of a phenotype-driven N-ethyl-N-nitrosourea (ENU) mutagenesis screen in mice for the identification of dominant mutations involved in the regulation and modulation of alcohol-drinking behavior. The chemical mutagen ENU was utilized in the generation of 131 male ENU-mutant C57BL/6J mice (G0). These ENU-treated mice were paired with wild-type C57BL/6J mice to generate G1 and subsequent generations. In total, 3327 mice were generated. Starting with G1, mice were screened for voluntary oral self-administration of 10% (v/v) alcohol vs. water in a two-bottle paradigm. From these mice, after a total period of 5 weeks of drinking, 43 mutants fulfilled the criteria of an "alcohol phenotype," that is, high or low ethanol intake. They were then selected for breeding and tested in a "confirmation cross" (G2-G4) for inheritance. Although we did not establish stable high or low drinking lines, several results were obtained in the context of alcohol consumption. First, female mice drank more alcohol than their male counterparts. Second, the former demonstrated greater infertility. Third, all animals displayed relatively stable alcohol intake, although significantly different in two different laboratories. Finally, seasonal and monthly variability was observed, with the highest alcohol consumption occurring in spring and the lowest in autumn. In conclusion, it seems difficult to identify dominant mutations involved in the modulation or regulation of voluntary alcohol consumption via a phenotype-driven ENU mutagenesis screen. In accordance with the findings from knockout studies, we suggest that mainly recessive mutations contribute to an alcohol-drinking or alcohol-avoiding phenotype.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0938-8990
e-ISSN 1432-1777
Journal Mammalian Genome
Quellenangaben Volume: 19, Issue: 2, Pages: 77-84 Article Number: , Supplement: ,
Publisher Springer
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)