Genetic Variability in Adenosine Deaminase‐Like Contributes to Variation in Alcohol Preference in Mice
HMB Lesscher, A Bailey… - Alcoholism: Clinical …, 2017 - Wiley Online Library
Alcoholism: Clinical and Experimental Research, 2017•Wiley Online Library
Background A substantial part of the risk for alcohol use disorder is determined by genetic
factors. We previously used chromosome substitution (CSS) mice, to identify a quantitative
trait loci (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 …
factors. We previously used chromosome substitution (CSS) mice, to identify a quantitative
trait loci (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 …
Background
A substantial part of the risk for alcohol use disorder is determined by genetic factors. We previously used chromosome substitution (CSS) mice, to identify a quantitative trait loci (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 CSS mice, to 4 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 3 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.
Conclusions
This study identifies Adal as a genetically protective factor against alcohol consumption in mice, in which elevated Adal levels contribute to low alcohol preference.
Wiley Online Library