Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick disease)

Cell. 1995 Jun 30;81(7):1053-61. doi: 10.1016/s0092-8674(05)80010-8.


We have generated an acid sphingomyelinase (aSMase)-deficient mouse line by gene targeting. This novel strain of mutant mouse mimics the lethal, neurovisceral form of the human sphingomyelin storage disease, known as Niemann-Pick disease. Homozygous mice accumulate sphingomyelin extensively in the reticuloendothelial system of liver, spleen, bone marrow, and lung, and in the brain. Most strikingly, the ganglionic cell layer of Purkinje cells of the cerebellum degenerates completely, leading to severe impairment of neuromotor coordination. The Niemann-Pick mouse might facilitate studies on the function of aSMase in the generation of ceramide as proposed second messenger in the intracellular signaling pathways and across the plasma membrane. Furthermore, it provides a suitable model for the development of strategies for somatic gene therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Southern
  • Bone Marrow / enzymology
  • Brain / enzymology*
  • Cells, Cultured
  • DNA / analysis
  • DNA Primers
  • Embryo, Mammalian
  • Homozygote
  • Humans
  • Liver / enzymology*
  • Lung / enzymology
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mononuclear Phagocyte System
  • Niemann-Pick Diseases / enzymology*
  • Niemann-Pick Diseases / genetics
  • Polymerase Chain Reaction
  • Purkinje Cells / enzymology
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Recombination, Genetic
  • Restriction Mapping
  • Sphingomyelin Phosphodiesterase / biosynthesis
  • Sphingomyelin Phosphodiesterase / deficiency*
  • Sphingomyelin Phosphodiesterase / genetics*
  • Spleen / enzymology*
  • Stem Cells / enzymology


  • DNA Primers
  • RNA, Messenger
  • DNA
  • Sphingomyelin Phosphodiesterase