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

  title={Acid sphingomyelinase deficient mice: a model of types A and B Niemann–Pick disease},
  author={Kenichi Horinouchi and Shai Erlich and Daniel P. Perl and Klaus Ferlinz and Charles L. Bisgaier and Konrad Sandhoff and Robert J. Desnick and Colin L Stewart and Edward H. Schuchman},
  journal={Nature Genetics},
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… 

Infusion of recombinant human acid sphingomyelinase into Niemann‐Pick disease mice leads to visceral, but not neurological, correction of the pathophysiology

It is indicated that ERT should be an effective therapeutic approach for Type B NPD, but is unlikely to prevent the severe neurodegeneration associated with Type A NPD.

Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of Niemann-Pick disease.

Alterations in surfactant composition, including increased sphingomyelin content, contributed to the abnormal surfactan function observed in the ASM-deficient mouse, and ASM is required for normal surfactants catabolism by alveolar macrophages in vivo.

The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann–Pick disease

  • E. Schuchman
  • Biology
    Journal of Inherited Metabolic Disease
  • 2007
Patients with types A and B Niemann–Pick disease (NPD) have an inherited deficiency of acid sphingomyelinase (ASM) activity, which appears to be more frequent in individuals of Middle Eastern and North African descent.

Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor

A relation between hippocampal cell differentiation defect, nSMase and VDR increase in NPA mice is suggested, and protein levels were enhanced, probably because of the slower protein degradation rate in this area.

Analysis of the Lung Pathology and Alveolar Macrophage Function in the Acid Sphingomyelinase–Deficient Mouse Model of Niemann-Pick Disease

It is demonstrated that the ASMKO mice can be used as a model to study the lung pathology associated with NPD, and that the cellular and biochemical analysis of pulmonary airspaces may be a useful approach to monitoring disease progression and/or treatment.

Phenotype of acid sphingomyelinase deficiency knockout mice

  • W. Stoffel
  • Biology
    Cell Death and Differentiation
  • 2001
The experiments described in this publication have been performed with mice from the asmase mouse line of at least 12 ± 16 weeks of age and older which have developed the histological and clinical manifestations of NPD: the alterations of the lipid composition of hepatocyte, splenocyte and fibroblast cell membranes as well as the consequences for cellular signal transduction pathways which parallel the increasing incorporation of sphingomyelin and the changes of the complex lipid compositionof plasmamembranes.

Elevation of lung surfactant phosphatidylcholine in mouse models of Sandhoff and of Niemann–Pick A disease

Results suggest that changes in phospholipid levels and composition in lung surfactant might be a general feature of sphingoipid storage diseases, which may be in part responsible for the increased susceptibility of these patients to respiratory infections and lung pathology.

Sphingosylphosphorylcholine in Niemann-Pick Disease Brain: Accumulation in Type A But Not in Type B

This study establishes the integrity of brain tissue in Niemann-Pick disease type B and suggests that the lysocompound Sphingosylphosphorylcholine could play a role in the pathophysiology of brain dysfunction in the neuronopathic type A.

Lack of Acid Sphingomyelinase Induces Age-Related Retinal Degeneration

The early outer retinal dysfunction, outer segment degeneration, accumulation of lipofuscin and autophagosome markers provide evidence that disruption of lysosomal function contributes to the age-dependent retinal degeneration exhibited by ASMase KO mice.



Retroviral-mediated transfer of the human acid sphingomyelinase cDNA: correction of the metabolic defect in cultured Niemann-Pick disease cells.

Retroviral-mediated gene transfer was used to introduce the full-length ASM cDNA into cultured fibroblasts from two unrelated type A NPD patients to provide further evidence that retroviral gene transfer may be used to correct the pathology of NPD cells.


Brain of a 14‐month‐old patient with the infantile form of Niemann Pick disease was found to be practically devoid of sphingomyelinase activity when assayed at pH 5.4, and in the presence of magnesium ions considerable hydrolysis of spindingomyelin was obtained by brain preparations.

Toward gene therapy for Niemann-Pick disease (NPD): separation of retrovirally corrected and noncorrected NPD fibroblasts using a novel fluorescent sphingomyelin.

Novel selection procedures were developed to separate retrovirally corrected and noncorrected NPD fibroblasts based on the receptor-mediated delivery of a fluorescently (pyrene)-labeled sphingomyelin to the lysosomes of cells using liposomes coated with apolipoprotein E.

Sphingomyelinase in normal human spleens and in spleens from subjects with Niemann-Pick disease.

Another enzyme, this one magnesium-dependent, capable of catalyzing the cleavage of sphingomyelin has been detected in the spleens of patients with the classical form of Niemann-Pick disease.

Human acid sphingomyelinase from human urine.

Purification and Characterization of Neutral and Acid Sphingomyelinases from Rat Brain

The neutral and acid sphingomyelinases probably consist of common polypeptides and are immunologically cross‐reactive.