Diclofenac toxicity in old world vultures is well described in the literature by both the severity of the toxicity induced and the speed of death. While the mechanism of toxicity remains unknown at present, the necropsy signs of gout suggests primary renal involvement at the level of the uric acid excretory pathways. From information in the chicken and man, uric acid excretion is known to be a complex process that involves a combination of glomerular filtration and active tubular excretion. For the proximal convoluted tubules excretion occurs as a two-step process with the basolateral cell membrane using the organic anion transporters and the apical membrane using the multidrug resistant protein to transport uric acid from the blood into the tubular fluid. With uric acid excretion seemingly inhibited by diclofenac, it becomes important to characterize these transporter mechanism at the species level. With no information being available on the molecular characterization/expression of MRPs of Gyps africanus, for this study we used next generation sequencing, and Sanger sequencing on the renal tissue of African white backed vulture (AWB), as the first step to establish if the MRPs gene are expressed in AWB. In silico analysis was conducted using different software to ascertain the function of the latter genes. The sequencing results revealed that the MRP2 and MRP4 are expressed in AWB vultures. Phylogeny of avian MRPs genes confirms that vultures and eagles are closely related, which could be attributed to having the same ancestral genes and foraging behavior. In silico analysis confirmed the transcribed proteins would transports anionic compounds and glucose.

中文翻译：

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多药耐药蛋白2和4在非洲白背秃鹫（Gyps Africanus）中的表达及系统发育

双氯芬酸对旧世界秃鹰的毒性在文献中通过引起的毒性的严重程度和死亡速度得到了很好的描述。虽然目前毒性机制尚不清楚，但痛风的尸检迹象表明尿酸排泄途径水平上的原发性肾脏受累。根据鸡和人的信息，已知尿酸排泄是一个复杂的过程，涉及肾小球滤过和活性肾小管排泄的组合。对于近曲小管，排泄作为两步过程发生，基底外侧细胞膜使用有机阴离子转运蛋白，顶端膜使用多重耐药蛋白将尿酸从血液转运到肾小管液中。由于尿酸排泄似乎受到双氯芬酸的抑制，在物种水平上表征这些转运蛋白机制变得很重要。由于没有关于 Gyps Africanus MRPs 的分子特征/表达的信息，在本研究中，我们使用了下一代测序和非洲白背秃鹫 (AWB) 肾组织的 Sanger 测序，作为确定是否MRPs 基因在 AWB 中表达。使用不同的软件进行计算机分析以确定后一基因的功能。测序结果显示MRP2和MRP4在AWB秃鹫中表达。鸟类MRPs基因的系统发育证实秃鹫和鹰密切相关，这可能归因于具有相同的祖先基因和觅食行为。计算机分析证实转录的蛋白质会运输阴离子化合物和葡萄糖。