The picture on the right depicts neurodegeneration in the fruitfly Drosophila melanogaster, caused by expression of a human protein in its compound eye. Mutations in this protein are responsible for the inherited neurodegenerative disorder Huntington's disease, and these flies should be a useful animal model for the human condition.

In fact, there is already a mouse model for Huntington's disease, so why do we need another? Writing in Neuron (21, 633-642; 1998), George R. Jackson et al. explain that, whereas mutant mice do not show much in the way of neuronal cell death, the flies show many of the same symptoms as humans.

Huntington's disease is caused by long tracts of the amino acid glutamine in a protein called huntingtin. In healthy people this protein contains a run of 37 or fewer glutamine residues. But in patients with Huntington's disease that number can exceed 150. Protein fragments containing the glutamine tracts are toxic to nerve cells, killing them through the formation of nuclear aggregates.

Might long glutamine tracts also cause neurodegeneration in Drosophila? To test this, Jackson and colleagues expressed fragments of human huntingtin complementary DNA containing 2, 75 or 120 consecutive glutamines in adult fly eyes. Drosophila eyes consist of an array of cell clusters called ommatidia (pictured right), each containing eight photoreceptor neurons. The authors found that expression of the 120-glutamine tract leads to rapid (within ten days) degeneration of the photoreceptor cells (pictured left). The 75-glutamine tract caused much less severe disruption after ten days, consistent with the human condition — the longer the repeat, the sooner the disease takes hold.

Jackson et al. also show that death is not blocked by expression of an anti-apoptotic protein, p35, suggesting that the death pathway is distinct from those already known in flies. But what could this pathway be? Perhaps the Drosophila model will help to answer these questions.