ArticleHuman molecular genetics2012
A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 129 citations in OpenAlex.
- Multi-omics reveal phosphatidic acid phosphatases modify Niemann-Pick type C disease severity.iScience · 2026Article
- Optimization of systemic AAV9 gene therapy in Niemann-Pick disease, type C1 mice.Life science alliance · 2026Article
- Unveiling Lipid Dysregulation: Lipidomics of Mouse Brain and Isolated Myelin in Niemann-Pick Disease Type C1.bioRxiv : the preprint server for biology · 2026Article
- Article
- Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome associated with alteration of metabolic signaling.American journal of human genetics · 2025Article
- Pathogenic variants inmedRxiv : the preprint server for health sciences · 2025Article
- Advances in mass spectrometry of lipids for the investigation of Niemann-pick type C disease.Lipids in health and disease · 2025Review
- Enhanced mGluRCell death & disease · 2024Article
- Endo-lysosomal dysfunction and neuronal-glial crosstalk in Niemann-Pick type C disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.Frontiers in pharmacology · 2024Review
- NPC1 is required for postnatal islet β cell differentiation by maintaining mitochondria turnover.Theranostics · 2024Article
- Reduced Cerebellar BDNF Availability Affects Postnatal Differentiation and Maturation of Granule Cells in a Mouse Model of Cholesterol Dyshomeostasis.Molecular neurobiology · 2023Article
- Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine.NPJ genomic medicine · 2023Review
- A Novel SmallCells · 2023Article
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Lithium ameliorates Niemann-Pick C1 disease phenotypes by impeding STING/SREBP2 activation.iScience · 2023Article
- Disruptive lysosomal-metabolic signaling and neurodevelopmental deficits that precede Purkinje cell loss in a mouse model of Niemann-Pick Type-C disease.Scientific reports · 2023Article
- The Cerebellum in Niemann-Pick C1 Disease: Mouse Versus Man.Cerebellum (London, England) · 2023Review
- Severe neurometabolic phenotype inFrontiers in molecular neuroscience · 2023Article
- Trehalose enhances mitochondria deficits in human NPC1 mutant fibroblasts but disrupts mouse Purkinje cell dendritic growth ex vivo.PloS one · 2023Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
We have identified a point mutation in Npc1 that creates a novel mouse model (Npc1(nmf164)) of Niemann-Pick type C1 (NPC) disease: a single nucleotide change (A to G at cDNA bp 3163) that results in an aspartate to glycine change at position 1005 (D1005G). This change is in the cysteine-rich luminal loop of the NPC1 protein and is highly similar to commonly occurring human mutations. Genetic and molecular biological analyses, including sequencing the Npc1(spm) allele and identifying a truncating mutation, confirm that the mutation in Npc1(nmf164) mice is distinct from those in other existing mouse models of NPC disease (Npc1(nih), Npc1(spm)). Analyses of lifespan, body and spleen weight, gait and other motor activities, as well as acoustic startle responses all reveal a more slowly developing phenotype in Npc1(nmf164) mutant mice than in mice with the null mutations (Npc1(nih), Npc1(spm)). Although Npc1 mRNA levels appear relatively normal, Npc1(nmf164) brain and liver display dramatic reductions in Npc1 protein, as well as abnormal cholesterol metabolism and altered glycolipid expression. Furthermore, histological analyses of liver, spleen, hippocampus, cortex and cerebellum reveal abnormal cholesterol accumulation, glial activation and Purkinje cell loss at a slower rate than in the Npc1(nih) mouse model. Magnetic resonance imaging studies also reveal significantly less demyelination/dysmyelination than in the null alleles. Thus, although prior mouse models may correspond to the severe infantile onset forms of NPC disease, Npc1(nmf164) mice offer many advantages as a model for the late-onset, more slowly progressing forms of NPC disease that comprise the large majority of human cases.
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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.