Drosophila study informs understanding of Wolfram syndrome 1

Sakakibara Y, Sekiya M, Fujisaki N, Quan X, Iijima KM. Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila. PLoS Genet. 2018 Jan 22;14(1):e1007196. PMID: 29357349; PMCID: PMC5794194.

From the abstract: "Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1), is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. ... the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. ... This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases."

Fly and human studies related to Wolfram syndrome

Jones MA, Amr S, Ferebee A, Huynh P, Rosenfeld JA, Miles MF, Davies AG, Korey CA, Warrick JM, Shiang R, Elsea SH, Girirajan S, Grotewiel M. Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease. Biol Open. 2014 Apr 4. pii: bio.20147559v1. PMID: 24705017.