The Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608, USA.
Genes Brain Behav. 2013 Feb;12(1):87-97. doi: 10.1111/j.1601-183X.2012.00834.x. Epub 2012 Aug 31.
Despite recent advances in the understanding of ethanol's biological action, many of the molecular targets of ethanol and mechanisms behind ethanol's effect on behavior remain poorly understood. In an effort to identify novel genes, the products of which regulate behavioral responses to ethanol, we recently identified a mutation in the dtao gene that confers resistance to the locomotor stimulating effect of ethanol in Drosophila. dtao encodes a member of the Ste20 family of serine/threonine kinases implicated in MAP kinase signaling pathways. In this study, we report that conditional ablation of the mouse dtao homolog, Taok2, constitutively and specifically in the nervous system, results in strain-specific and overlapping alterations in ethanol-dependent behaviors. These data suggest a functional conservation of dtao and Taok2 in mediating ethanol's biological action and identify Taok2 as a putative candidate gene for ethanol use disorders in humans.
尽管最近在理解乙醇的生物学作用方面取得了进展,但许多乙醇的分子靶点以及乙醇对行为影响的机制仍知之甚少。为了确定调节对乙醇行为反应的新型基因,我们最近在 dtao 基因中发现了一个突变,该突变使果蝇对乙醇的运动刺激作用产生抗性。dtao 编码丝氨酸/苏氨酸激酶 Ste20 家族的一个成员,该家族参与 MAP 激酶信号通路。在这项研究中,我们报告说,条件性剔除小鼠 dtao 同源物 Taok2,在神经系统中持续且特异性地表达,会导致特定于品系和重叠的乙醇依赖行为改变。这些数据表明 dtao 和 Taok2 在介导乙醇的生物学作用方面具有功能上的保守性,并将 Taok2 确定为人类乙醇使用障碍的一个潜在候选基因。