This report describes arthrogryposis, renal dysfunction, and cholestasis 1 (ARCS1), which is a subtype of ARC syndrome; ARCS1 exhibits autosomal recessive inheritance. The human gene implicated in this disease is VPS33B, a protein involved in trafficking and sorting of lysosomal proteins. There is a single moderate-scoring fly ortholog, Vps33B, for which an amorphic allele and RNAi targeting constructs have been generated.
The human VPS33B gene has not been introduced into flies.
Animals homozygous for an amorphic mutation of Dmel\Vps33B are viable and fertile, but phagosomal maturation and function is impaired. Vps33B mutant flies exhibit extreme sensitivity to infections with non-pathogenic E. coli; the cause of death does not appear to be the bacterial load itself, but exaggerated anti-microbial responses to non-pathogenic microbes. This response mimics the recurrent sepsis that can contribute to death in ARC patients. Physical interactions of Dmel\Vps33B have been described; see below and in the Vps33B gene report.
[updated Nov. 2017 by FlyBase; FBrf0222196]