Long sleep and short sleep mice differ in nicotine-stimulated 86Rb+ efflux and alpha4 nicotinic receptor subunit cDNA sequence.

Long sleep and short sleep mice differ in nicotine-stimulated 86Rb+ efflux and alpha4 nicotinic receptor subunit cDNA sequence.
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长睡眠和短睡眠小鼠在尼古丁刺激的 86Rb 流出和 α4 烟碱受体亚基 cDNA 序列上存在差异。

DOI:
10.1097/00008571-200106000-00008
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发表时间:
2001
期刊:
Pharmacogenetics
影响因子:
--
通讯作者:
Collins,AC
Collins,AC
中科院分区:
--
文献类型:
--
作者:
Stitzel,JA;Dobelis,P;Jimenez,M;Collins,AC

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在最近的一项研究中,我们报道了与 α 4 烟碱受体基因 (Chrna4) 相关的限制性片段长度多态性可能在调节 LS 和 SS 小鼠系对尼古丁癫痫发作诱导作用的差异敏感性中发挥作用。由于 α 4 亚基 (CHRNA4) 通常与 β 2 亚基 (CHRNB2) 形成异聚体,因此对来自 LS 和 SS 小鼠的 α 4 和 β 2 cDNA 进行了克隆和测序。发现α 4 基因编码部分存在多态性(1587A 至 G),这应导致第 529 位(T529A)发生苏氨酸/丙氨酸取代。 LS 和 SS β2 烟碱受体亚基 cDNA 是相同的。使用离子 (86 Rb+) 通量测定评估了 α 4 多态性的潜在后果,该测定可能测量 α 4 β 2 型受体的功能。当不包含牛血清白蛋白 (BSA) 时,可观察到最大尼古丁刺激离子通量的 LS-SS 差异,但当灌注缓冲液中包含 BSA 时,未观察到这种差异。目前的证据表明,BSA 可能会改变处于基态和脱敏形式的烟碱受体的比例。因此,Chrna4 T529A 取代可能导致两种受体形式的比例差异,从而促进受体功能的差异以及对尼古丁的不同行为敏感性。
In a recent study, we reported that a restriction fragment length polymorphism associated with the α 4 nicotinic receptor gene (Chrna4) may play a role in regulating differential sensitivity of LS and SS mouse lines to the seizure-inducing effects of nicotine. Since the α 4 subunit (CHRNA4) is often found as a heteromer with the β 2 subunit (CHRNB2), α 4 and β 2 cDNAs from the LS and SS mice were cloned and sequenced. A polymorphism in the coding portion of the α 4 gene was found (1587A to G) which should result in a threonine/alanine substitution at position 529 (T529A). The LS and SS β 2 nicotinic receptor subunit cDNAs were identical. The potential consequences of the α 4 polymorphism were evaluated using an ion (86 Rb+) flux assay that likely measures the function of α 4 β 2-type receptors. LS–SS differences in maximal nicotine-stimulated ion flux were seen when bovine serum albumin (BSA) was not included but this difference was not seen when BSA was included in the perfusion buffer. Current evidence suggests that BSA may alter the ratio of nicotinic receptors that are in the ground state and desensitized forms. Thus, it may be that the Chrna4 T529A substitution leads to a difference in the ratio of the two receptor forms which then promotes differences in receptor function, as well as differential behavioural sensitivity to nicotine.
长睡眠和短睡眠小鼠杂交对尼古丁和乙醇反应的经典遗传分析。
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发表时间: 1998
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