A phenotypic perspective on mammalian oxygen sensor candidates
A phenotypic perspective on mammalian oxygen sensor candidates
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DOI：
10.1196/annals.1353.024
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发表时间：
2006-01-01
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影响因子：
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通讯作者：
Baysal, Bora E.
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文献类型：
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作者：
Baysal, Bora E.
哺乳动物慢性低氧刺激可引起多种表型改变，如红细胞增多症、肺血管改变、肺动脉高压和颈动脉小体(CB)增大。这些表型变化为测试氧传感器候选是否参与有机体对环境缺氧的反应提供了依据。在这里，我评估了几个通常被认为是氧传感器候选的表型证据。NADPH氧化酶、线粒体复合体I、III、IV和血红素加氧酶2基因的种系突变会导致不同的表型结果，表明不同的生理作用而不是氧气感知。VHL和HIF1 Pro羟基酶2基因的胚系突变导致红细胞增多症，这与它们在氧稳态中的作用一致。然而，目前还不清楚影响氧气可获得性的环境变化是否会改变它们的表型，就像氧传感器的缺陷所预期的那样。琥珀酸脱氢酶(SDH)；线粒体复合体II)胚系突变可导致CB副神经节瘤，有证据表明副神经节瘤的严重程度和群体遗传学可能受海拔的影响。因此，从表型的角度来看，琥珀酸脱氢酶(SDH)似乎是一个得到很好支持的氧传感器候选基因。有人建议，一个通用的氧传感器候选者必须得到来自多层生物复杂性的证据的支持。
Chronic hypoxic stimulation in mammals can induce several phenotypic changes, such as polycythemia, pulmonary vascular changes, pulmonary hypertension, and carotid body (CB) enlargement. These phenotypic alterations provide a toot to test whether an oxygen sensor candidate is involved in an organism's response to environmental hypoxia. Here I evaluate the phenotypic evidence for several commonly considered oxygen sensor candidates. Germline mutations in NADPH oxidase, mitochondrial complexes I, III, IV, and heme oxygenase 2 genes cause different phenotypic consequences, suggesting distinct physiological roles rather than oxygen sensing. Germline mutations in VHL and HIF1 prolyl hydroxylase 2 genes cause polycythemia consistent with their role in oxygen homeostasis. However, it is unclear whether environmental variations affecting oxygen availability modify their phenotype, as would be expected from a defect in an oxygen sensor. Succinate dehydrogenase (SDH); mitochondrial complex II) germline mutations cause CB paragangliomas and there is evidence that the severity and the population genetics of paragangliomas may be influenced by altitude. Thus, from a phenotypic perspective, succinate dehydrogenase (SDH) appears to be a well-supported oxygen sensor candidate. It is suggested that a universal oxygen sensor candidate must be supported by evidence from multiple layers of biological complexity.