This report describes fly models of neurodegenerative disease using alleles of the fly gene Vps13, which is a vacuolar protein sorting-associated protein. There are two highly related genes in human, VPS13A and VPS13C, both of which are implicated in neurodegenerative disease: VPS13A is implicated in chorea-acanthocytosis (MIM:200150, FBhh0000592) and VPS13C is implicated in Parkinson disease 23 (MIM:616840, FBhh0000624). There are additional members of the VPS family in both species. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Vps13.
A UAS construct of the wild-type human Hsap\VPS13A gene has been introduced into flies. Partial heterologous rescue (functional complementation) of the Dmel\Vps13 loss-of-function phenotypes is observed. The human VPS13C gene has not been introduced into flies.
A temperature-sensitive loss-of-function allele of Dmel\Vps13 results in decreased survival to adult stage, decreased life span post-eclosion, progressive locomotor defects in the adult stage, and abnormalities in the larval and adult CNS. RNAi-mediated knockdown of Vps13 enhances neurodegeneration phenotypes observed for a fly genotype representing a model of Parkinson disease 1 model (FBhh0000006). A small number of genetic and physical interactions of Dmel\Vps13 have been described; see below and in the Vps13 gene report.
[updated Sep. 2017 by FlyBase; FBrf0222196]
Many to one: 2 human to 1 Drosophila; other lower-scoring orthologs in both species. The two closely related human genes are VPS13A and VPS13C.
Many to one: 2 human to 1 Drosophila; other lower-scoring orthologs in both species. The two closely related human genes are VPS13A and VPS13C.
High-scoring ortholog of human VPS13A; moderate-scoring ortholog of VPS13C (1 Drosophila to 2 human); other lower-scoring orthologs in both species. Dmel\Vps13 shares 28-30% identity and 45-50% similarity with the human genes.
