Olfactory marker protein (OMP) gene deletion causes altered physiological activity of olfactory sensory neurons
Olfactory marker protein (OMP) gene deletion causes altered physiological activity of olfactory sensory neurons
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DOI：
10.1073/pnas.93.18.9858
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发表时间：
1996-09-03
影响因子：
11.1
通讯作者：
Margolis, FL
中科院分区：
文献类型：
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作者：
Buiakova, OI;Baker, H;Margolis, FL
嗅觉标记蛋白（Olfactory marker protein，OMP）是一种在成熟的嗅神经元中表达的丰富的、在遗传学上保守的、功能未知的胞质蛋白。为了解决其功能，我们通过胚胎干细胞中的基因靶向产生了OMP缺陷小鼠。我们报告说，这些OMP基因敲除小鼠对气味刺激的反应能力受到损害，从而为OMP功能提供了深入了解。嗅觉神经上皮细胞对几种气味的最大嗅觉电图反应在突变体中比对照小20-40%。此外，在无效小鼠中，乙酸异戊酯刺激后的发作和恢复动力学延长。此外，与对照组相比，在一定浓度范围内，该能力受损。这些结果意味着指向嗅球的神经活动也减少了。在OMP敲除小鼠中观察到的延髓表型与该假设一致。酪氨酸羟化酶，儿茶酚胺生物合成的限速酶，和神经肽胆囊收缩素的含量分别减少了65%和50%的延髓活性。这种相似性的外周嗅觉传入阻滞或鼻孔阻滞诱导的基因表达的突触后变化证实，功能性神经活动减少的嗅神经上皮细胞和嗅神经投射到球中的OMP-null小鼠。这些观察结果提供了有力的支持的结论，OMP是一种新的气味检测/信号转导级联的调制组件。
Olfactory marker protein (OMP) is an abundant, phylogenetically conserved, cytoplasmic protein of unknown function expressed almost exclusively in mature olfactory neurons. To address its function, we generated OMP-deficient mice by gene targeting in embryonic stem cells. We report that these OMP-null mice are compromised in their ability to respond to odor stimuli, providing insight to OMP function. The maximal electroolfactogram response of the olfactory neuroepithelium to several odorants was 20-40% smaller in the mutants compared with controls. In addition, the onset and recovery kinetics following isoamyl acetate stimulation are prolonged in the null mice. Furthermore, the ability is impaired, over a range of concentrations, compared with controls. These results imply that neural activity directed toward the olfactory bulb is also reduced. The bulbar phenotype observed in the OMP-null mouse is consistent with this hypothesis. Bulbar activity of tyrosine hydroxylase, the rate limiting enzyme of catecholamine biosynthesis, and content of the neuropeptide cholecystokinin are reduced by 65% and 50%, respectively. This similarity to postsynaptic changes in gene expression induced by peripheral olfactory deafferentation or naris blockade confirms that functional neural activity is reduced in both the olfactory neuroepithelium and the olfactory nerve projection to the bulb in the OMP-null mouse. These observations provide strong support for the conclusion that OMP is a novel modulatory component of the odor detection/signal transduction cascade.