Zebrafish embryos have emerged as an attractive model to study kidney development. Nick Hastie has a medium size fish facility supported by 2 full-time assistants. His lab has generated GFP-transgeneic reporter strains to mark specific renal cell types and to follow lineage commitment. Here, he will perform a pilot mutageneisis screen to identify genes that regulate renal development.
Xenopus is another lower vertebrate model that represents a simple model of nephron development. André Brändli has extensive experience using this model system to study key genes in renal development and he runs the largest state-of-the-art Xenopus facility in Switzerland. Here, we will establish a gene expression atlas of the developing and the adult kidney by large scale in situ hybridzation to map expression of Xenopus orthologues of genes expressed in the mammalian kidney.
Mice are the higher vertebrate model of choice to perform genetic manipulation and test gene function in vivo. Approximately half the participating groups have experience in generating mouse models. Here, we will use both systematic mutagenesis and candidate gene targeting to explore disease genes. In systematic approaches Roger Cox will use ENU mutagenesis in mice and sperm to produce models at large scale. In terms of candiadate genes, many partners will apply gene inactivation to study loss of gene function; generate GFP-reporter lines to map cell fate during development, and use tissue-secific overexpression to dissect the contribution of genes to disease processes in glomerulosclerosis and tubular acidosis. Nick Hastie and Andreas Schedl will develop novel murine cell line and organ cultures as alternative experimental systems to study renal development and function.
Rats offer disease models that recapitulate many features of genetic complexity and pathophysiology of disease processes seen in patients. Giuseppe Remuzzi and Friedrich Luft will use spontaneous rat models of proteinuric renal injury and transgenic rat models of hypertension induced renal damage to analyze candidate genes in common renal injury processes.