PDF(Pubmed)
Abstract：
The Olfr78 gene encodes a G-protein-coupled olfactory receptor that is expressed in several ectopic sites. Olfr78 is one of the most abundant mRNA species in carotid body (CB) glomus cells. These cells are the prototypical oxygen (O2) sensitive arterial chemoreceptors, which, in response to lowered O2 tension (hypoxia), activate the respiratory centers to induce hyperventilation. It has been proposed that Olfr78 is a lactate receptor and that glomus cell activation by the increase in blood lactate mediates the hypoxic ventilatory response (HVR). However, this proposal has been challenged by several groups showing that Olfr78 is not a physiologically relevant lactate receptor and that the O2-based regulation of breathing is not affected in constitutive Olfr78 knockout mice. In another study, constitutive Olfr78 knockout mice were reported to have altered systemic and CB responses to mild hypoxia. To further characterize the functional role of Olfr78 in CB glomus cells, we here generated a conditional Olfr78 knockout mouse strain and then restricted the knockout to glomus cells and other catecholaminergic cells by crossing with a tyrosine hydroxylase-specific Cre driver strain (TH-Olfr78 KO mice). We find that TH-Olfr78 KO mice have a normal HVR. Interestingly, glomus cells of TH-Olfr78 KO mice exhibit molecular and electrophysiological alterations as well as a reduced dopamine content in secretory vesicles and neurosecretory activity. These functional characteristics resemble those of CB neuroblasts in wild-type mice. We suggest that, although Olfr78 is not essential for CB O2 sensing, activation of Olfr78-dependent pathways is required for maturation of glomus cells.
摘要：
Olfr78基因编码在几个异位位点表达的G蛋白偶联嗅觉受体。Olfr78是颈动脉体（CB）glomus细胞中最丰富的mRNA之一。这些细胞是典型的氧（O2）敏感的动脉化学感受器，which,响应降低的O2张力（缺氧），激活呼吸中枢以引起过度换气。已经提出Olfr78是乳酸受体，并且通过血液乳酸增加而激活的血管球细胞介导了低氧通气反应（HVR）。然而,这项建议受到了几个小组的挑战,这些小组表明Olfr78不是生理相关的乳酸受体,并且在组成型Olfr78敲除小鼠中,基于O2的呼吸调节不受影响.在另一项研究中,据报道，组成型Olfr78敲除小鼠对轻度缺氧的全身和CB反应发生了改变。为了进一步表征Olfr78在CBglomus细胞中的功能作用，我们在这里产生了条件Olfr78敲除小鼠品系,然后通过与酪氨酸羟化酶特异性Cre驱动品系(TH-Olfr78KO小鼠)杂交,将敲除限制在glomus细胞和其他儿茶酚胺能细胞中.我们发现TH-Olfr78KO小鼠具有正常的HVR。有趣的是,TH-Olfr78KO小鼠的glomus细胞表现出分子和电生理改变，分泌囊泡和神经分泌活性中的多巴胺含量降低。这些功能特征类似于野生型小鼠中CB神经母细胞的功能特征。我们建议,虽然Olfr78对于CBO2传感不是必需的，Olfr78依赖性途径的激活是血管球细胞成熟所必需的。
