MICE DEFICIENT IN LYSOSOMAL ACID-PHOSPHATASE DEVELOP LYSOSOMAL STORAGE IN THE KIDNEY AND CENTRAL-NERVOUS-SYSTEM

Lysosomal acid phosphatase (LAP) is a tartrate-sensitive enzyme with u biquitous expression. Neither the physiological substrates nor the fun ctional significance is known. Mice with a deficiency of LAP generated by targeted disruption of the LAP gene are fertile and develop normal ly. Microscopic examination of various peripheral organs revealed prog redient lysosomal storage in podocytes and tubular epithelial cells of the kidney, with regionally different ultrastructural appearance of t he stored material. Within the central nervous system, lysosomal stora ge was detected to a regionally different extent in microglia, ependym al cells, and astroglia concomitant with the development of a progress ive astrogliosis and microglial activation. Whereas behavioral and neu romotor analyses were unable to distinguish between control and defici ent mice, similar to 7% of the deficient animals developed generalized seizures. From the age of 6 months onward, conspicuous alterations of bone structure became apparent, resulting in a kyphoscoliotic malform ation of the lower thoracic vertebral column. We conclude from these f indings that LAP has a unique function in only a subset of cells, wher e its deficiency causes the storage of a heterogeneously appearing mat erial in lysosomes. The causal relationship of the enzyme defect to th e clinical manifestations remains to be determined.