title: Pathology of visceral organs and bone marrow in an acid sphingomyelinase deficient knock-out mouse line, mimicking human Niemann-Pick disease type A. A light and electron microscopic study.
abstract: A recently generated aSmase knock-out mouse line develops a lethal storage disease which mimics the neurovisceral form of Niemann-Pick disease in man. In extension to the previously described neuropathological changes, the purpose of this study was to provide a detailed morphological, particularly ultrastructural analysis of the visceral organs of these animals including spleen, liver, intestine, lung, and kidney along with a sequential histological investigation of the bone marrow. Our results showed a progressive lysosomal storage as indicated by an increasing amount of foam cells in the bone marrow with age, extending to all visceral organs. Most severe storage phenomena were found in the mononuclear-macrophage system, however, parenchymal cells of visceral organs were also markedly involved. The ultrastructural appearance of membrane-bound inclusions displayed a pleomorphic aspect ranging from small vesicular and vesiculo-granular structures to huge lysosomes with membranous material deposited in lamellar or stacked arrays. The obvious similarity to its human counterpart along with an easy availability makes this animal model a valuable tool for further studies of Niemann-Pick disease type A.
authors.affiliation: Institute of Pathology, Medical Faculty, University of Cologne, Germany.
authors.forename: T A
authors.initials: TA
authors.lastname: Kuemmel
authors.forename: J
authors.initials: J
authors.lastname: Thiele
authors.forename: R
authors.initials: R
authors.lastname: Schroeder
authors.forename: W
authors.initials: W
authors.lastname: Stoffel
mesh_terms: D000375:Aging; D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D004195:Disease Models, Animal; D005487:Foam Cells / Q000648:ultrastructure; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure; D016464:Lysosomal Storage Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009542:Niemann-Pick Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D013045:Species Specificity; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014781:Viscera / Q000473:pathology*
chemical_list: D013108:Sphingomyelin Phosphodiesterase