• retinal disease

A number of retinal diseases are associated with defects in the PROM1 gene, which encodes prominin 1, a transmembrane glycoprotein that appears to have multiple roles in cell differentiation and proliferation. There are two fly orthologs, prom, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated, and promL, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis are available. The two Drosophila orthologs show different stage- and tissue-specific expression patterns. Although most highly expressed in the developing adult eye, promL is expressed in many tissues and developmental stages. Expression of prom is more restricted, primarily to the adult eye and during late pupal stage in the developing eye.

Many of the human genes associated with retinal disease are implicated in multiple related diseases, such as retinitis pigmentosa, cone-rod dystrophy, macular degeneration, and Stargardt disease. In some cases, a single molecular variant is implicated in more than one form of retinal disease. PROM1 is implicated in retinitis pigmentosa 41 (MIM:612095; FBhh0000203), retinal macular dystrophy 2 (MIM:608051; FBhh0000217), cone-rod dystrophy 12 (MIM:612657; FBhh0000570), and Stargardt disease 4 (MIM:603786).

UAS constructs of the human Hsap\PROM1 gene have been introduced into flies, including wild-type and a variant carrying a mutational lesions implicated in disease (see the 'Disease-Implicated Variants' table, below). Expression of wild-type PROM1 in the developing eye results in heterologous rescue (functional complementation) of loss-of-function Dmel\prom mutant phenotypes. Variant(s) implicated in human disease tested (as transgenic human gene, PROM1): the R373C variant form has been introduced into flies; this variant is implicated in three of the diseases associated with PROM1, retinal macular dystrophy 2 (MCDR2), Stargardt disease 4 (STGD4), and cone-rod dystrophy 12 (CRD12).

Loss-of-function mutations in the Dmel\prom gene result in abnormalities in the structure of the adult eye, producing fused rhabdomeres. Phenotypic assays using mutations of the Dmel\prom gene have allowed characterization of genetic interactions. Mutations of promL have not been well characterized.

[updated Aug. 2021 by FlyBase; FBrf0222196]