JCI：用TRAP小鼠检测急性肾损伤

　　

生物通报道：目前，南加州大学（USC）的干细胞科学家，建立了一种“TRAP小鼠”来捕获肾衰竭的早期症状，相关研究结果发表在最近的《Journal of Clinical Investigation》杂志。他们的新转基因小鼠品系，使用一种称为TRAP的技术，从各种实体器官中提取细胞和遗传信息。

在2008年11月出版的《细胞》（Cell）上，美国洛克菲勒医学研究所的科学家们提出了一种全新的细胞特异性标记技术，将一种荧光标签附加到目的细胞的蛋白质生产机器——核糖体上。然后，科学家们可以收集标记的核糖体，确定哪些活性基因正在命令这些核糖体生产蛋白质。科学家们将这种基因标记方法称为翻译核糖体亲和纯化（translating ribosome affinity purification，TRAP）。相关阅读：Cell:新型神经细胞特异性标记技术。

继这项突破性进展之后，近日南加州大学Andy McMahon 实验室高级研究助理Jing Liu带领的研究小组，通过制备一种TRAP小鼠，而使这项技术变得更加简单和更容易接近。当与现有的数千只转基因小鼠品系中的任何一只进行杂交后，TRAP小鼠产生的小鼠后代，在其特定器官或细胞类型中具有标记的核糖体。

为了演示这可能如何有用，Liu和她的同事使用TRAP小鼠，来标记四种不同类型的肾脏细胞，并确定了急性肾损伤的早期信号。

因为手术、感染或药物毒性，有5%到7%的住院患者经历了急性肾损伤，这可能会导致慢性肾脏疾病或死亡。

目前，医生只能在急性肾损伤发生一整天之后才能检测到它。TRAP小鼠使医生能够更早地检测到肾损伤，这将大大提高患者的健康状况。

Liu说：“这项技术很简单，肾脏领域对于我们的这个研究结果感到非常兴奋。我们预计，TRAP小鼠将促进我们对很多疾病和许多不同器官系统损伤的细胞和分子认识。”

（生物通：王英）

生物通推荐原文摘要：
Cell-specific translational profiling in acute kidney injury
Abstract：Acute kidney injury (AKI) promotes an abrupt loss of kidney function that results in substantial morbidity and mortality. Considerable effort has gone toward identification of diagnostic biomarkers and analysis of AKI-associated molecular events; however, most studies have adopted organ-wide approaches and have not elucidated the interplay among different cell types involved in AKI pathophysiology. To better characterize AKI-associated molecular and cellular events, we developed a mouse line that enables the identification of translational profiles in specific cell types. This strategy relies on CRE recombinase–dependent activation of an EGFP-tagged L10a ribosomal protein subunit, which allows translating ribosome affinity purification (TRAP) of mRNA populations in CRE-expressing cells. Combining this mouse line with cell type–specific CRE-driver lines, we identified distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Twenty-four hours following IRI, distinct translational signatures were identified in the nephron, kidney interstitial cell populations, vascular endothelium, and macrophages/monocytes. Furthermore, TRAP captured known IRI-associated markers, validating this approach. Biological function annotation, canonical pathway analysis, and in situ analysis of identified response genes provided insight into cell-specific injury signatures. Our study provides a deep, cell-based view of early injury-associated molecular events in AKI and documents a versatile, genetic tool to monitor cell-specific and temporal-specific biological processes in disease modeling.