THE EFFECT OF LYSOSOMOTROPIC AMINES ON BEIGE MOUSE CELLS

The beige mutant in the mouse is characterized by enlarged lysosomes i n many cell types due to increased fluidity of cellular membranes and organelle fusion. In this study, mutant fibroblasts derived from C57BL / 6J;bg(J)/bg(J) animals were compared with control fibroblasts (C57BL /6J;+/+) for vacuolation when treated with lysosomotropic weak bases i ncluding ammonium chloride, trimethylamine, and methylamine. These ami nes produce vacuolation by their accumulation in cellular acidic compa rtments, which causes osmotic swelling and fusion of organelles due to the increase in pH. Beige cells exhibited greater vacuolation than co ntrol cells for all treatments, which was indicative of the mutant's e ffect on organelle fusion and membrane fluidity. Trimethylamine caused the most pronounced difference in vacuolation between mutant and cont rol cells. This method allows for a simple morphological distinction b etween beige and control cells that also utilizes a physiological diff erence in the expression of the beige gene. (C) 1997 Academic Press.