• neurodegenerative disease

This report describes a model of neurodegenerative disease using the Drosophila gene Shawn. There are two human orthologs of this gene, SLC25A39 and SLC25A40, which encode mitochondrial carrier proteins. Classical loss-of-function mutations, RNAi targeting constructs, and an amorphic mutation caused by imprecise excision of a TE insertion have been generated for Dmel\Shawn.

The human Hsap\SLC25A40 gene has been introduced into flies, but has not been characterized. As of this update, human SLC25A39 has not been introduced into flies.

In a Drosophila screen for mutations resulting in defective ERG (electroretinogram) response, several mutations within the Shawn gene were recovered. The Shawn protein localizes to mitochondria; loss of function leads to an accumulation of reactive oxygen species that cause mitochondrial morphological and functional defects. Progressive neurodegeneration of photoreceptor terminals and degeneration of postsynaptic muscle cells at the larval neuromuscular junction are observed. Loss of Shawn results in increased manganese and calcium levels and an increase in mitochondrial free iron.

Several other human disease models in fly address metal toxicity and brain iron overload in neurodegenerative disease; see 'neurodegeneration with brain iron accumulation' (FBhh0000223), 'Parkinson-like disease, metal toxicity' (FBhh0000884) and 'Parkinson disease, iron overload' (FBhh0000885).

[updated Oct. 2019 by FlyBase; FBrf0222196]