ArticleMolecular genetics and metabolism2008
Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models.
Article in Molecular genetics and metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 55 citations in OpenAlex.
- Retention of lysosomal acid sphingomyelinase protects from Niemann-Pick Disease.Neurobiology of disease · 2025Article
- Ceramide lowering rescues respiratory defects in a Drosophila model of acid sphingomyelinase deficiency.Human molecular genetics · 2024Article
- The impact of sphingomyelin on the pathophysiology and treatment response to olipudase alfa in acid sphingomyelinase deficiency.Genetics in medicine open · 2024Review
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Solving the secretory acid sphingomyelinase puzzle: Insights from lysosome-mediated parasite invasion and plasma membrane repair.Cellular microbiology · 2019Review
- Characterization of Niemann-Pick diseases genes mutation spectrum in Iran and identification of a novel mutation inMedical journal of the Islamic Republic of Iran · 2019Article
- A Robust Liposomal Platform for Direct Colorimetric Detection of Sphingomyelinase Enzyme and Inhibitors.ACS nano · 2018Article
- Metabolic etiologies in West syndrome.Epilepsia open · 2018Review
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- Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B.European journal of human genetics : EJHG · 2016Article
- Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages.The Journal of biological chemistry · 2014Article
- Orphazyme.Nature biotechnology · 2013Article
- The Acid Sphingomyelinase Sequence Variant p.A487V Is Not Associated With Decreased Levels of Enzymatic Activity.JIMD reports · 2013Article
- The roles of neutral sphingomyelinases in neurological pathologies.Neurochemical research · 2012Review
- Cathepsin B overexpression due to acid sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease.The Journal of biological chemistry · 2012Article
- Brain pathology in Niemann Pick disease type A: insights from the acid sphingomyelinase knockout mice.Journal of neurochemistry · 2011Review
- Multivesicular bodies in neurons: distribution, protein content, and trafficking functions.Progress in neurobiology · 2011Review
- A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing.The Journal of biological chemistry · 2011Article
- Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation.The Journal of biological chemistry · 2010Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Herein we describe detailed characterization of four common mutations (L302P, H421Y, R496L and DeltaR608) within the acid sphingomyelinase (ASM) gene causing types A and B Niemann-Pick disease (NPD). In vitro and in situ enzyme assays revealed marked deficiencies of ASM activity in NPD cell lines homoallelic for each mutation, although Western blotting and fluorescent microscopy showed that the mutant ASM polypeptides were expressed at normal levels and trafficked to lysosomes. Co-immunoprecipitation of the polypeptides with the ER chaperone, BiP, confirmed these findings, as did in vitro expression of the mutant cDNAs in reticulocyte lysates. We further developed a computer assisted, three-dimensional model of human ASM based on homologies to known proteins, and used this model to map each NPD mutation in relation to putative substrate binding, hydrolysis and zinc-binding domains. Lastly, we generated transgenic mice expressing the R496L and DeltaR608 mutations on the complete ASM knock-out background (ASMKO), and established breeding colonies for the future evaluation of enzyme enhancement therapies. Analysis of these mice demonstrated that the mutant ASM transgenes were expressed at high levels in the brain, and in the case of the DeltaR608 mutation, produced residual ASM activity that was significantly above the ASMKO background.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.