title: 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.
authors.affiliation: Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universität Göttingen, Gosslerstrasse 12D, 37073 Göttingen, Federal Republic of Germany. saftig@uni-bc2.gwd.de
authors.forename: P
authors.initials: P
authors.lastname: Saftig
authors.forename: D
authors.initials: D
authors.lastname: Hartmann
authors.forename: R
authors.initials: R
authors.lastname: Lüllmann-Rauch
authors.forename: J
authors.initials: J
authors.lastname: Wolff
authors.forename: M
authors.initials: M
authors.lastname: Evers
authors.forename: A
authors.initials: A
authors.lastname: Köster
authors.forename: M
authors.initials: M
authors.lastname: Hetman
authors.forename: K
authors.initials: K
authors.lastname: von Figura
authors.forename: C
authors.initials: C
authors.lastname: Peters
mesh_terms: D000135:Acid Phosphatase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001842:Bone and Bones / Q000002:abnormalities; D002402:Cathepsin D / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000201:enzymology* / Q000473:pathology; D005347:Fibroblasts / Q000201:enzymology; D007674:Kidney Diseases / Q000201:enzymology* / Q000473:pathology; D016464:Lysosomal Storage Diseases / Q000201:enzymology*; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000201:enzymology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000201:enzymology / Q000473:pathology; D010641:Phenotype; D012640:Seizures / Q000201:enzymology; D013644:Tartrates / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D013644:Tartrates; D000135:Acid Phosphatase; D002402:Cathepsin D; C029768:tartaric acid