Nat Commun:Gabrb1可能是酗酒关键基因

2013-11-29 MedSci MedSci原创

英国科学家Anstee QM等发现,Gabrb1基因控制老鼠的饮酒行为,一旦修改基因,几乎滴酒不沾的老鼠居然开始酗酒。该基因是GABA受体(GABAAR)β1亚单位基因。研究者采用N-ethyl-N-nitrosourea诱导广泛突变的模型中发现酗酒动物而进行研究。该基因L285R位点突变后,GABA离子通道被激活,增加对GABAR受体敏感性。另一个突变位点P228H也能导致酗酒。

英国科学家Anstee QM等发现,Gabrb1基因控制老鼠的饮酒行为,一旦修改基因,几乎滴酒不沾的老鼠居然开始酗酒。该基因是GABA受体(GABAAR)β1亚单位基因。研究者采用N-ethyl-N-nitrosourea诱导广泛突变的模型中发现酗酒动物而进行研究。该基因L285R位点突变后,GABA离子通道被激活,增加对GABAR受体敏感性。另一个突变位点P228H也能导致酗酒。

科学家把一杯水和一杯稀释的酒放在正常的老鼠面前,任其挑选,结果它们几乎滴酒不沾,全都喜欢喝水。不过,科学家修改老鼠的Gabrb1基因后,它们的喜好为之一变:喜欢喝酒,而不爱喝水。它们的饮酒量甚至达到每天摄入水分的85%。

英国帝国理工学院霍华德 托马斯教授带领的研究团队发现Gabrb1能改变生物对酒精的偏好。老鼠的基因被修改以后,它们酷爱酒精,对水则置之不理,甚至愿意花力气推动杠杆喝酒。这还不是一时心血来潮,因为老鼠会一直这样做。有时候,老鼠还会饮酒过量,醉到肢体行动都不听使唤。

纽卡斯尔大学的昆廷 安斯蒂说:“只是稍微改变一个基因中的编码,就能显著影响摄取酒精这种复杂的行为。真让人惊讶。我们还要继续工作,看这个基因是否对人也有类似影响……我们有机会将来找出有效治疗酗酒行为的方法。”

原始出处:
Anstee QM, Knapp S, Maguire EP, Hosie AM, Thomas P, Mortensen M, Bhome R, Martinez A, Walker SE, Dixon CI, Ruparelia K, Montagnese S, Kuo YT, Herlihy A, Bell JD, Robinson I, Guerrini I, McQuillin A, Fisher EM, Ungless MA, Gurling HM, Morgan MY, Brown SD, Stephens DN, Belelli D, Lambert JJ, Smart TG, Thomas HC. Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition. Nat Commun. 2013 Nov 26;4:2816. doi: 10.1038/ncomms3816.

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    2014-07-14 liuli5079
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    2013-12-03 liye789132251