Loss-of-function mutations in sodium channel Nav1.7 cause anosmia.
Loss-of-function mutations in sodium channel Nav1.7 cause anosmia.
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DOI：
10.1038/nature09975
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发表时间：
2011-04-14
期刊：
影响因子：
64.8
通讯作者：
Zufall, Frank
中科院分区：
文献类型：
--
作者：
Weiss, Jan;Pyrski, Martina;Jacobi, Eric;Bufe, Bernd;Willnecker, Vivienne;Schick, Bernhard;Zizzari, Philippe;Gossage, Samuel J.;Greer, Charles A.;Leinders-Zufall, Trese;Woods, C. Geoffrey;Wood, John N.;Zufall, Frank
编码电压门控钠通道Nav1.7的基因SCN9A功能丧失，导致人类先天无法体验疼痛。在这里，我们展示了Nav1.7不仅是痛觉所必需的，也是老鼠和人类嗅觉所必需的。我们检查了SCN9A功能缺失突变的人类患者，发现他们无法感觉气味。为了确定Nav1.7在气味感知中的重要作用，我们产生了条件性空白小鼠，其中Nav1.7从所有嗅觉感觉神经元中移除。在没有Nav1.7的情况下，这些神经元仍然产生气味诱发的动作电位，但不能从嗅觉系统中第一个突触的轴突终末启动突触信号。突变小鼠不再表现出重要的气味引导行为，如天生气味识别和回避、短期气味学习和母体幼崽取回。我们的研究建立了一种先天性全身嗅觉障碍的小鼠模型，并为探索人类嗅觉的遗传基础提供了新的策略。
Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Nav1.7, causes a congenital inability to experience pain in humans. Here we show that Nav1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Nav1.7 in odour perception, we generated conditional null mice in which Nav1.7 was removed from all olfactory sensory neurons. In the absence of Nav1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.
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