Functional genomics of chlorine-induced acute lung injury in mice.
Functional genomics of chlorine-induced acute lung injury in mice.
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DOI：
10.1513/pats.201001-005sm
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发表时间：
2010-07-01
期刊：
影响因子：
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通讯作者：
Prows, Daniel R
中科院分区：
文献类型：
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作者：
Leikauf, George D;Pope-Varsalona, Hannah;Prows, Daniel R
急性肺损伤可以间接诱导（例如，脓毒症）或直接（例如，氯吸入）。由于治疗仍然限于支持性措施，死亡率仍然很高（约74，500例死亡/年）。在过去，意外（铁路脱轨）和故意（伊拉克恐怖主义）氯暴露导致急性肺损伤死亡和住院治疗。为了更好地了解控制氯诱导的急性肺损伤的分子事件，我们已经开发了一种功能基因组学方法，使用近交系小鼠品系。将各种小鼠品系暴露于氯（45 ppm x 24 h），并监测存活率。最不同的菌株的平均生存时间变化超过三倍，支持潜在的易感性遗传基础的可能性。这些不同的菌株是额外的遗传分析，以确定控制氯诱导的急性肺损伤的关键候选基因的优秀模型。然后，基因靶向小鼠可用于测试易感性候选基因的功能意义，这在揭示急性肺损伤生物学的新见解方面可能是有价值的。
Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury.