• kidney disease

The Drosophila orthologs of cubilin and amnionless are specifically expressed in nephrocytes, which function in both filtration and protein reabsorption. The role of the cubilin/amnionless receptor complex in flies appears to be analogous to that of human cubilin/amnionless receptor complex in the proximal tubules of the kidney [reviewed in FBrf0220711 and FBrf0235870; see also the human disease model report 'kidney disease (fly models overview)' FBhh0000738]. The human gene that encodes cubilin is CUBN; there is a single high-scoring ortholog in Drosophila, Cubn, for which RNAi-targeting constructs have been generated. There is a second moderate-scoring ortholog in flies, Cubn2, for which RNAi-targeting constructs, CRISPR/Cas9 mediated loss-of-function mutations, and alleles caused by insertional mutagenesis have been generated.

The human CUBN gene has not been introduced into flies.

The expression of Dmel\Cubn is restricted to the fly nephrocytes. Using a driver specific for expression in pericardial nephrocytes, RNAi-effected knockdown of Cubn blocks uptake of a protein marker into the nephrocyte. Knockdown of Cubn does not cause significant changes in viability under normal conditions, however, under conditions of toxin stress viability is significantly reduced. In animals homozygous for Cubn2 loss-of-function mutations, nephrocytes lose their characteristic morphological features and supernumerary slit diaphragm structures are found in the interior of the cell; nephrocyte endocytosis is compromised. It is postulated that the Drosophila cubilin/amnionless receptor complex is a tripartite complex formed by the products of Cubn, Cubn2 and amn.

See also the disease model reports for kidney disease (postulated), AMN-related (FBhh0000551) and megaloblastic anemia 1 (MGA1, FBhh0000082).

[updated Feb. 2022 by FlyBase; FBrf0222196]