This report describes cystic renal dysplasia, susceptibility to (CYSRD). CYSRD has been described as exhibiting autosomal dominant inheritance with incomplete penetrance; it may exhibit a genetic maternal effect. The human gene implicated in this disease is BicC family RNA binding protein 1 (BICC1) which plays a role in regulating protein translation during embryonic development. There is a single orthologous gene in Drosophila, BicC, for which multiple genetic reagents have been generated including classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis.
The human BICC1 gene has not been introduced into flies.
Animals hemizygous (mutation over a deficiency) for loss-of-function mutations of Dmel\BicC show reduced survival rate and display progressive abnormalities of the Malpighian tubules, including disorganization of the tubular epithelial cells and large, often numerous cysts. (Insect Malpighian tubules serve the same functions as the vertebrate kidney; see FBrf0235307.) Females heterozygous for loss-of-function mutations are semi-sterile, with non-hatching embryos exhibiting a bicaudal phenotype or head defects. Physical and genetic interactions of Dmel\BicC have been described; see below and in the BicC gene report.
This disease model has been used in drug discovery, most notably using mimics of second mitochondria-derived activator of caspases (Smac).
[updated Feb. 2021 by FlyBase; FBrf0222196]
[RENAL DYSPLASIA, CYSTIC, SUSCEPTIBILITY TO; CYSRD](https://omim.org/entry/601331)
[BICC FAMILY RNA-BINDING PROTEIN 1; BICC1](https://omim.org/entry/614295)
Renal dysplasia, defined as abnormal metanephric differentiation, has variable presentations that cover a spectrum of conditions, including hypoplasia, multicystic dysplasia, and aplasia. Overall, renal dysplasia is the leading cause of end-stage renal disease in children (https://emedicine.medscape.com/article/982560-overview).
Susceptibility to the development of cystic renal dysplasia (CYSRD) can be conferred by heterozygous mutation in the BICC1 gene. In studies to date, implicated mutations are inherited from an unaffected parent, suggesting that the disorder shows incomplete penetrance or that additional genetic or environmental factors are necessary for its development. [from MIM:601331; 2017.12.04]
BICC1 (BicC family RNA binding protein 1) encodes an RNA-binding protein that is active in regulating gene expression by modulating protein translation during embryonic development. Studies in mouse show the BICC1 protein to be a maternally-provided gene product. [Gene Cards, BICC1; 2017.12.05]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human BICC1 (1 Drosophila to 1 human); Dmel\BicC shares 31% identity and 47% similarity with the human gene.
