ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
A murine Niemann-Pick C1 I1061T knock-in model recapitulates the pathological features of the most prevalent human disease allele.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 126 citations in OpenAlex.
- Article
- Multi-omics reveal phosphatidic acid phosphatases modify Niemann-Pick type C disease severity.iScience · 2026Article
- Short-lived Niemann-Pick type C mice with accelerated brain aging as a novel model for Alzheimer's disease research.Neural regeneration research · 2026Article
- Optimization of systemic AAV9 gene therapy in Niemann-Pick disease, type C1 mice.Life science alliance · 2026Article
- Generation and characterization of human iPSC-derivedbioRxiv : the preprint server for biology · 2026Article
- Unveiling Lipid Dysregulation: Lipidomics of Mouse Brain and Isolated Myelin in Niemann-Pick Disease Type C1.bioRxiv : the preprint server for biology · 2026Article
- HSP25 and HSP25-P-Ser15 Prompt Innate Neuroprotection in Lobe X of the Cerebellum.International journal of molecular sciences · 2026Article
- Host sphingolipids supportmBio · 2025Article
- Advances in mass spectrometry of lipids for the investigation of Niemann-pick type C disease.Lipids in health and disease · 2025Review
- Exploration of Bromodomain Proteins as Drug Targets for Niemann-Pick Type C Disease.International journal of molecular sciences · 2025Article
- Article
- Review
- Mutant induced neurons and humanized mice enable identification of Niemann-Pick type C1 proteostatic therapies.JCI insight · 2024Article
- Endogenous Protein-Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex.Journal of proteome research · 2024Article
- Accumulation of alkyl-lysophosphatidylcholines in Niemann-Pick disease type C1.Journal of lipid research · 2024Article
- Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models.Cell death & disease · 2024Article
- Collaborative Cross mice have diverse phenotypic responses to infection with Methicillin-resistant Staphylococcus aureus USA300.PLoS genetics · 2024Article
- Sterol O-Acyltransferase 1 (International journal of molecular sciences · 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
27 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Niemann-Pick Type C1 (NPC1) disease is a rare neurovisceral, cholesterol-sphingolipid lysosomal storage disorder characterized by ataxia, motor impairment, progressive intellectual decline, and dementia. The most prevalent mutation, NPC1(I1061T), encodes a misfolded protein with a reduced half-life caused by ER-associated degradation. Therapies directed at stabilization of the mutant NPC1 protein reduce cholesterol storage in fibroblasts but have not been tested in vivo because of lack of a suitable animal model. Whereas the prominent features of human NPC1 disease are replicated in the null Npc1(-/-) mouse, this model is not amenable to examining proteostatic therapies. The objective of the present study was to develop an NPC1 I1061T knock-in mouse in which to test proteostatic therapies. Compared with the Npc1(-/-) mouse, this Npc1(tm(I1061T)Dso) model displays a less severe, delayed form of NPC1 disease with respect to weight loss, decreased motor coordination, Purkinje cell death, lipid storage, and premature death. The murine NPC1(I1061T) protein has a reduced half-life in vivo, consistent with protein misfolding and rapid ER-associated degradation, and can be stabilized by histone deacetylase inhibition. This novel mouse model faithfully recapitulates human NPC1 disease and provides a powerful tool for preclinical evaluation of therapies targeting NPC1 protein variants with compromised stability.
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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.