Genetic variability in adenosine deaminase-like contributes to variation in alcohol preference in mice

Autor: Lesscher, HMB, Bailey, A, Vanderschuren, LJMJ
Jazyk: angličtina
Rok vydání: 2017
ISSN: 1530-0277
Popis: BACKGROUND: A substantial part of the risk for alcohol use disorder (AUD) is determined by genetic factors. We previously used chromosome substitution (CSS) mice, to identify a QTL for alcohol preference on mouse chromosome 2. The aim of this study was to identify candidate genes within this QTL that confer the risk for alcohol preference. METHODS: In order to delineate the neurobiological underpinnings of alcohol consumption, we expanded on the QTL approach to identify candidate genes for high alcohol preference in mice. We narrowed down a QTL for alcohol preference on mouse chromosome 2, that we previously identified using chromosome substitution (CSS) mice, to four candidate genes in silico. Expression levels of these candidate genes in prefrontal cortex, amygdala and nucleus accumbens, brain regions implicated in reward and addiction, were subsequently compared for the CSS-2 and the C57BL/6J host strain. RESULTS: We observed increased expression of adenosine deaminase-like (Adal) in all three regions in CSS-2 mice. Moreover, we found that the adenosine deaminase inhibitor EHNA reduced the difference in alcohol preference between CSS-2 and C57Bl/6J mice. CONCLUSION: The current study identifies Adal as a genetically protective factor against alcohol consumption in mice, in which elevated Adal levels contribute to low alcohol preference. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE