Morphological alterations in the inner ear of the arylsulfatase A-deficient mouse

Metachromatic leukodystrophy of humans is an inherited sulfatide lipidosis due to deficiency of arylsulfatase A (ASA). As an animal model, ASA(-/-) mi ce have been generated. A previous study showed that the mice lose most of their spiral (acoustic) ganglion cells and develop deafness by the end of t he first year of life. The present report describes the sulfatide histochem istry and ultrastructure of the inner ears of ASA(-/-) mice at 0.5-26 month s of age. Lysosomal accumulation of sulfatides was observed in various cell types such as Schwann cells that maintain the myelin sheaths around the sp iral and vestibular ganglion cells, periaxonal Schwann cells, macrophages, and spiral and vestibular ganglion cell perikarya. In the spiral ganglion, the only surviving neurons were those which are primarily non-myelinated (t ype 2 cells). However, the myelinated spiral neurons and their processes we re rarely encountered within the process of dying, suggesting that this was a rather rapid process. Since the myelin sheaths around dying perikarya an d axons appeared structurally normal, the primary cause of the neuronal cel l death seems to reside in the neuron. In contrast to the spiral ganglion, the vestibular ganglion as a whole survived throughout the period of observ ation. The organ of Corti and the vestibular apparatus appeared preserved a t the light microscopic level, despite massive sulfatide storage in the ves tibular hair cells.