Hitzemann Robert, Oberbeck Denesa, Iancu Ovidiu, Darakjian Priscila, McWeeney Shannon, Spence Stephanie, Schlumbohm Jason, Metten Pamela, Crabbe John
Oregon Health & Science University, Portland, OR, USA; Veterans Affairs Portland Health Care System, Portland, OR, USA.
Oregon Health & Science University, Portland, OR, USA.
Alcohol. 2017 May;60:115-120. doi: 10.1016/j.alcohol.2017.02.176. Epub 2017 Apr 12.
Among animals at risk for excessive ethanol consumption such as the HDID selected mouse lines, there is considerable individual variation in the amount of ethanol consumed and the associated blood ethanol concentrations (BECs). For the HDID lines, this variation occurs even though the residual genetic variation associated with the DID phenotype has been largely exhausted and thus is most likely associated with epigenetic factors. Here we focus on the question of whether the genes associated with individual variation in HDID-1 mice are different from those associated with selection (risk) (Iancu et al., 2013). Thirty-three HDID-1 mice were phenotyped for their BECs at the end of a standard DID trial, were sacrificed 3 weeks later, and RNA-Seq was used to analyze the striatal transcriptome. The data obtained illustrate that there is considerable overlap of the risk and variation gene sets, both focused on the fine-tuning of synaptic plasticity.
在有过度乙醇消费风险的动物中,如选择的HDID小鼠品系,乙醇摄入量和相关血液乙醇浓度(BEC)存在相当大的个体差异。对于HDID品系,即使与DID表型相关的残余遗传变异已基本耗尽,这种变异仍然存在,因此很可能与表观遗传因素有关。在这里,我们关注的问题是,与HDID - 1小鼠个体差异相关的基因是否与选择(风险)相关的基因不同(Iancu等人,2013年)。在标准DID试验结束时,对33只HDID - 1小鼠的BEC进行了表型分析,3周后将其处死,并使用RNA测序分析纹状体转录组。获得的数据表明,风险基因集和变异基因集有相当大的重叠,两者都集中在突触可塑性的微调上。