65 Mammalian models like the mouse and rat are considered extremely valuable models of disease that typically mimic human conditions.

Their anatomy and cell biology are well conserved and techniques such as genetic fate mapping can facilitate the tracking of cell types during regeneration. Furthermore, these models are essential to evaluate efficacy and toxicity of pharmaceuticals for AKI treatment, and remain the gold standard in preclinical trials. Rodent AKI models include IRI as well as exposure to chemical agents such as gentamicin and, thus, can be used to model the outcomes of different insults.66 However, scientists are still faced with several limitations when studying AKI in these mammalian

kidneys. Access to the rodent kidney requires surgery. For the Buparlisib in vivo most part, this eliminates real-time visual monitoring of the renal tissues in living animals, with the only current exception being a very small population of renal tubules and vessels near the surface of the organ.67 For a number of reasons, the zebrafish has emerged as a relevant vertebrate that can be used to address several voids in the AKI field. Research in zebrafish embryos and adults has shown that the pronephros and mesonephros kidney forms, respectively, are valid models for gentamicin-based AKI studies.68, 69, 70, 71, 72 and 73 Zebrafish nephrons in embryos and adult animals show a conserved

make-up with mammals (detailed further in following sections).10 and 74 Zebrafish larvae are optically transparent, allowing microscopic observation Smad3 signaling along the entire length of the kidney. Additionally, zebrafish serve as a suitable experimental model in that they breed frequently, produce large numbers of progeny, and the embryos develop ex utero. 75 They also progress very rapidly through embryogenesis and organogenesis. C1GALT1 For example, the embryonic kidney has formed 1 day after fertilization and the pronephric tubules begin filtration of the blood by the second day of life. 76 One important aspect of AKI research resides in the possibility of identifying small molecules with therapeutic potential to aid in repair and regeneration. The zebrafish has become an appealing tool for such small molecule screens.75, 77 and 78 Because the embryo is small in size, relatively small quantities of compounds are needed for testing, and embryos can be kept alive for days without added nutrients because they utilize maternal food deposits. The adult zebrafish can be injected with small amounts of compounds to interrogate regeneration because of the small adult mass,79 enabling findings from the embryo to be tested in an adult organ setting. Comparable screening of pharmaceutical molecules in rodents would require an extraordinary amount of time, chemical compounds, as well as residential space.