A spontaneously immortalized Schwann cell line to study the molecular aspects of metachromatic leukodystrophy.

Abstract

The arylsulfatase A (ASA)-deficient mouse is a murine model of human metachromatic leukodystrophy (MLD) caused by a genetic defect in the ASA gene. Deficiency of ASA causes accumulation of cerebroside-3-sulfate (sulfatide) in visceral organs and in the central and peripheral nervous system, which subsequently causes demyelination in these areas. To investigate further the cellular pathomechanism of MLD, we established spontaneously immortalized Schwann cell lines from ASA-deficient mice. Cells showed marked sulfatide storage in the late endosomal/lysosomal compartment. This sulfatide accumulation can be further increased by external treatment with sulfatide using a lipid based transfection reagent as a cargo. The accumulated sulfatide was degraded in response to ASA treatment and first examination revealed that alteration on the molecular level found in ASA-deficient mice can also be observed in the presented cell culture model. Hence, these cells could be a suitable model to study MLD at a molecular level.