• kidney disease

This report describes a potential disease model, kidney disease (postulated), CDC42-related. The Drosophila Cdc42 gene was identified in a screen for fly genes required for the function of nephrocytes. (Nephrocytes are cells functionally analogous to the podocytes and proximal tubules of the vertebrate kidney.) Dmel\Cdc42 is orthologous to the human gene CDC42, which is a member of the Rho family of small GTPases. Rho GTPases participate in the regulation of a wide variety of signal transduction pathways and play a key role in cytoskeleton organization. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Cdc42.

The human Hsap\CDC42 gene has been introduced into flies, but has not been characterized in the context of this disease model.

Dmel\Cdc42 is expressed in all developmental stages; it is expressed ubiquitously in embryos. Animals homozygous for loss-of-function alleles of Cdc42 die during the embryonic stage. Using a driver specific for expression in pericardial nephrocytes, RNAi-effected knockdown of Cdc42 blocks uptake of a protein marker into the nephrocyte. Many physical and genetic interactions of Dmel\Cdc42 have been described; see below and in the Cdc42 gene report.

There is evidence using mouse models that the loss of the ortholog of CDC42 (Cdc42 in mouse) in podocytes results in nephropathy and renal failure (Scott et al., 2012, pubmed:22518006; Huang et al., 2016, pubmed:26986510).

[updated Jun. 2017 by FlyBase; FBrf0222196]