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

A recently generated aSmase knock-out mouse line develops a lethal sto rage disease which mimics the neurovisceral form of Niemann-Pick disea se in man. In extension to the previously described neuropathological changes, the purpose of this study was to provide a detailed morpholog ical, particularly ultrastructural analysis of the visceral organs of these animals including spleen, liver, intestine, lung, and kidney alo ng with a sequential histological investigation of the bone marrow. Ou r results showed a progressive lysosomal, storage as indicated by an i ncreasing amount of foam cells in the bone marrow with age, extending to all visceral organs. Most severe storage phenomena were found in th e mononuclear-macrophage system, however, parenchymal cells of viscera l organs were also markedly involved. The ultrastructural appearance o f membrane-bound inclusions displayed a pleomorphic aspect ranging fro m small vesicular and vesiculo-granular structures to huge lysosomes w ith membranous material deposited in lamellar or stacked arrays. The o bvious similarity to its human counterpart along with an easy availabi lity makes this animal model a valuable tool for further studies of Ni emann-Pick disease type A.