An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.
An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.
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DOI：
10.1371/journal.pone.0022636
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Heberlein U
中科院分区：
文献类型：
--
作者：
Lasek AW;Lim J;Kliethermes CL;Berger KH;Joslyn G;Brush G;Xue L;Robertson M;Moore MS;Vranizan K;Morris SW;Schuckit MA;White RL;Heberlein U
间变性淋巴瘤激酶（Alk）是在神经系统中表达的基因，其编码受体酪氨酸激酶，通常已知其在各种人类癌症中的致癌功能。我们已经确定Alk与果蝇、小鼠和人类对乙醇的行为反应改变有关。在dAlk中含有转座子插入的突变果蝇表现出对乙醇镇静作用的抗性增加。数据库分析显示，重组近交系小鼠脑中的Alk表达水平与乙醇诱导的共济失调和乙醇消耗量呈负相关。因此，我们测试了Alk基因敲除小鼠，发现它们对高剂量乙醇的反应更长，并且比野生型小鼠消耗更多的乙醇。最后，人类ALK的测序发现了与对乙醇的低水平反应相关的四种多态性，这是一种预测未来酒精使用障碍（AUDs）的中间表型。这些结果表明，Alk在乙醇相关行为中起着进化保守的作用。此外，ALK可能是一个新的候选基因，赋予AUDs的风险，以及药物干预的潜在目标。
Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention.
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DOI：
10.1111/j.1530-0277.2009.01093.x
发表时间：
2010-02
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Kong EC;Allouche L;Chapot PA;Vranizan K;Moore MS;Heberlein U;Wolf FW
通讯作者：
Wolf FW
影响因子：
4
作者：
Gouzi, JY;Moog-Lutz, C;Brunet-de Carvalho, N
通讯作者：
Brunet-de Carvalho, N
影响因子：
3.3
作者：
Kunugi, H.;Hashimoto, R.;Saitoh, O.
通讯作者：
Saitoh, O.
DOI：
10.1111/j.1530-0277.1996.tb01063.x
发表时间：
1996-02-01
影响因子：
3.2
作者：
Gill, K;Liu, Y;Deitrich, RA
通讯作者：
Deitrich, RA
影响因子：
2.3
作者：
Camicella, Sebastien;Amamoto, Ryoji;Ron, Dorit
通讯作者：
Ron, Dorit