• motor neuron disease

Based on characterization of the mouse wobbler mutation (a missense mutation in the Mmus\Vps54 gene), it has been postulated that destabilizing mutations of VPS54 result in motor neuron disease phenotypes. VPS54 encodes a component of the GARP complex and is involved in retrograde transport from early and late endosomes to the trans-Golgi network. There is a single orthologous gene in Drosophila, scat, for which multiple genetic reagents have been generated including null mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis.

Neither the human VPS54 gene nor the mouse Vps54 gene has been introduced into flies.

In adults, loss of Dmel\scat results in significantly shortened lifespan, reduced body size, and age-progressive defects in muscle mass and locomotor function; females exhibit stronger phenotypes; males are sterile. In larvae, a null mutation or motor-neuron-specific knockdown of scat results in neuromuscular junction overgrowth. Over-expression of Dmel\Rab7 was found to affect the larval phenotypes (see FBhh0000085).

[updated Dec. 2021 by FlyBase; FBrf0222196]