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 Bat ten disease gene. We have reported previously that deletion of BTN1, btn1-D elta, resulted in a pH-dependent resistance to D-(-)-threo-2-amino-1-[p-nit rophenyl]-1,3-propanediol (ANP). This phenotype was caused by btn1-Delta st rains having an elevated ability to acidify growth medium through an elevat ed activity of the plasma membrane H+-ATPase, resulting from a decreased va cuolar pH during early growth. We have determined that growing btn1-Delta s trains in the presence of chloroquine reverses the resistance to ANP, decre ases the rate of medium acidification, decreases the activity of plasma mem brane 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 strain s continue to grow. This phenotypic reversal of btn1-Delta can be considere d for developing a therapy far Batten disease.