Phenotypic reversal of the btn1 defects in yeast by chloroquine: a yeast model for Batten disease.

BTN1 of Saccharomyces cerevisiae encodes an ortholog of CLN3, the human Batten disease gene. We have reported previously that deletion of BTN1, btn1-Delta, resulted in a pH-dependent resistance to D-(-)-threo-2-amino-1-[p-nitrophenyl]-1,3-propanediol (ANP). This phenotype was caused by btn1-Delta strains having an elevated ability to acidify growth medium through an elevated activity of the plasma membrane H(+)-ATPase, resulting from a decreased vacuolar pH during early growth. We have determined that growing btn1-Delta strains in the presence of chloroquine reverses the resistance to ANP, decreases the rate of medium acidification, decreases the activity of plasma membrane H(+)-ATPase, and elevates vacuolar pH. However, an additional effect of this phenotypic reversal is that activity of plasma membrane H(+)-ATPase is decreased further and vacuolar pH is increased further as btn1-Delta strains continue to grow. This phenotypic reversal of btn1-Delta can be considered for developing a therapy for Batten disease.