Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
INSERM UMR1163, Laboratory of Epithelial Biology and Disease, Imagine Institute, Université de Paris, Hôpital Necker-Enfants Malades, Paris, France.
Nat Rev Nephrol. 2022 Jul;18(7):417-434. doi: 10.1038/s41581-022-00561-4. Epub 2022 Apr 11.
Although the genetic basis of many kidney diseases is being rapidly elucidated, their experimental study remains problematic owing to the lack of suitable models. The fruitfly Drosophila melanogaster provides a rapid, ethical and cost-effective model system of the kidney. The unique advantages of D. melanogaster include ease and low cost of maintenance, comprehensive availability of genetic mutants and powerful transgenic technologies, and less onerous regulation, as compared with mammalian systems. Renal and excretory functions in D. melanogaster reside in three main tissues - the transporting renal (Malpighian) tubules, the reabsorptive hindgut and the endocytic nephrocytes. Tubules contain multiple cell types and regions and generate a primary urine by transcellular transport rather than filtration, which is then subjected to selective reabsorption in the hindgut. By contrast, the nephrocytes are specialized for uptake of macromolecules and equipped with a filtering slit diaphragm resembling that of podocytes. Many genes with key roles in the human kidney have D. melanogaster orthologues that are enriched and functionally relevant in fly renal tissues. This similarity has allowed investigations of epithelial transport, kidney stone formation and podocyte and proximal tubule function. Furthermore, a range of unique quantitative phenotypes are available to measure function in both wild type and disease-modelling flies.
尽管许多肾脏疾病的遗传基础正在迅速阐明，但由于缺乏合适的模型，其实验研究仍然存在问题。果蝇 Drosophila melanogaster 为肾脏提供了一种快速、符合伦理道德且具有成本效益的模型系统。与哺乳动物系统相比，D. melanogaster 具有独特的优势，包括易于维护且成本低廉、全面的遗传突变体可用性和强大的转基因技术，以及监管要求不那么繁琐。果蝇的肾脏和排泄功能位于三个主要组织中 - 运输性肾（马氏管）小管、吸收性后肠和内吞性肾细胞。小管包含多种细胞类型和区域，并通过细胞间转运产生初级尿液，而不是通过过滤，然后在后肠中进行选择性再吸收。相比之下，肾细胞专门用于摄取大分子，并配备有类似于足细胞的过滤裂隙隔膜。许多在人类肾脏中具有关键作用的基因在果蝇中有其同源基因，这些基因在果蝇的肾脏组织中富集且具有功能相关性。这种相似性使得可以研究上皮细胞转运、肾结石形成以及足细胞和近端小管的功能。此外，还可以获得一系列独特的定量表型，以测量野生型和疾病建模果蝇中的功能。
