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Acid sphingomyelinase deficient mice: a model of types A and B Niemann–Pick disease

Nature Genetics volume 10, pages 288–293 (1995)Cite this article

Abstract

Types A and B Niemann–Pick disease (NPD) result from the deficient activity 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 of age. Analysis of these animals showed their tissues had no detectable ASM activity, the blood cholesterol levels and sphingomyelin in the liver and brain were elevated, and atrophy of the cerebellum and marked deficiency of Purkinje cells was evident. Microscopic analysis revealed NPD ‘cells’ in reticuloendothelial organs and characteristic NPD lesions in the brain. Thus, the ASM deficient mice should be of great value for studying the pathogenesis and treatment of NPD, and for investigations into the role of ASM in signal transduction and apoptosis.

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Authors and Affiliations

  1. Department of Human Genetics and Mount Sinai School of Medicine, 100th St. and Fifth Ave., Box 1203, New York, New York, 10029, USA

    Kenichi Horinouchi, Shai Erlich, Robert J. Desnick & Edward H. Schuchman

  2. Department of Pathology, Mount Sinai School of Medicine, 100th St. and Fifth Ave., Box 1203, New York, New York, 10029, USA

    Daniel P. Perl

  3. Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany

    Klaus Ferlinz & Konrad Sandhoff

  4. Department Atherosclerosis Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Ann Arbor, Michigan, 48105, USA

    Charles L. Bisgaier

  5. Department of Cell Biology and Developmental Biology, Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey, 07110, USA

    Colin L. Stewart

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  1. Kenichi Horinouchi
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Horinouchi, K., Erlich, S., Perl, D. et al. Acid sphingomyelinase deficient mice: a model of types A and B Niemann–Pick disease. Nat Genet 10, 288–293 (1995). https://doi.org/10.1038/ng0795-288

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