Juvenile neuronal ceroid lipofuscinosis (JNCL) is a lysosomal storage disorder in which neurodegeneration causes blindness, seizures, and mental and physical decline, eventually leading to death in early adulthood. CLN3 mutations cause JNCL, but CLN3 function is not yet known. Here, Rebecca Haines and colleagues use the fission yeast Schizosaccharomyces pombe to model human JNCL, by expressing CLN3 mutations in the yeast orthologue Btn1p. The mutations caused vacuole deficits analogous to the lysosome deficits of lipofuscinoses and, for each CLN3 mutation modeled, the severity of the yeast phenotype paralleled the severity of the human JNCL symptoms. The work presented here establishes a yeast model for mechanisms underlying JNCL and for screening novel therapeutic agents to treat this disease.

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2009