ACID SPHINGOMYELINASE DEFICIENT MICE - A MODEL OF TYPE-A AND TYPE-B NIEMANN-PICK DISEASE

Types A and B Niemann-Pick disease (NPD) result from the deficient act ivity of acid sphingomyelinase (ASM). An animal model of NPD has been created by gene targeting. In affected animals, the disease followed a severe, neurodegenerative course and death occurred by eight months o f age. Analysis of these animals showed their tissues had no detectabl e ASM activity, the blood cholesterol levels and sphingomyelin in the liver and brain were elevated, and atrophy of the cerebellum and marke d deficiency of Purkinje cells was evident. Microscopic analysis revea led 'NPD cells' in reticuloendothelial organs and characteristic NPD l esions in the brain. Thus, the ASM deficient mice should be of great v alue for studying the pathogenesis and treatment of NPD, and for inves tigations into the role of ASM in signal transduction and apoptosis.