Mice deficient in lysosomal acid phosphatase develop lysosomal storage in the kidney and central nervous system.

Abstract

Lysosomal acid phosphatase (LAP) is a tartrate-sensitive enzyme with ubiquitous expression. Neither the physiological substrates nor the functional significance is known. Mice with a deficiency of LAP generated by targeted disruption of the LAP gene are fertile and develop normally. Microscopic examination of various peripheral organs revealed progredient lysosomal storage in podocytes and tubular epithelial cells of the kidney, with regionally different ultrastructural appearance of the stored material. Within the central nervous system, lysosomal storage was detected to a regionally different extent in microglia, ependymal cells, and astroglia concomitant with the development of a progressive astrogliosis and microglial activation. Whereas behavioral and neuromotor analyses were unable to distinguish between control and deficient mice, approximately 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 malformation of the lower thoracic vertebral column. We conclude from these findings that LAP has a unique function in only a subset of cells, where its deficiency causes the storage of a heterogeneously appearing material in lysosomes. The causal relationship of the enzyme defect to the clinical manifestations remains to be determined.

7 Figures and Tables

01020'01'03'05'07'09'11'13'15'17
Citations per Year

92 Citations

Semantic Scholar estimates that this publication has 92 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Saftig1997MiceDI, title={Mice deficient in lysosomal acid phosphatase develop lysosomal storage in the kidney and central nervous system.}, author={Paul Saftig and D. Hartmann and Renate L{\"{u}llmann-Rauch and Jens E. Wolff and Margaret Evers and Antonia K{\"{o}ster and Michal Hetman and Kurt von Figura and C Peters}, journal={The Journal of biological chemistry}, year={1997}, volume={272 30}, pages={18628-35} }