Gene Symbol: Npc1
Description: NPC intracellular cholesterol transporter 1
Alias: A430089E03Rik, C85354, D18Ertd139e, D18Ertd723e, lcsd, nmf164, spm, NPC intracellular cholesterol transporter 1, Niemann-Pick C1 protein, Niemann-Pick type C1, niemann-Pick C1 protein, sphingomyelinosis
Species: mouse
Products:     Npc1

Top Publications

  1. Wasser C, Ertunc M, Liu X, Kavalali E. Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling. J Physiol. 2007;579:413-29 pubmed
    ..These results suggest that synaptic cholesterol balances evoked and spontaneous neurotransmission by hindering spontaneous synaptic vesicle turnover and sustaining evoked exo-endocytosis. ..
  2. Xie X, Brown M, Shelton J, Richardson J, Goldstein J, Liang G. Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice. Proc Natl Acad Sci U S A. 2011;108:15330-5 pubmed publisher
    Substitution mutations in adjacent amino acids of the N-terminal domain of NPC1, a lysosomal membrane protein, abolish its cholesterol binding activity and impair its ability to export cholesterol from lysosomes of cultured cells lacking ..
  3. Pentchev P, Comly M, Kruth H, Patel S, Proestel M, Weintroub H. The cholesterol storage disorder of the mutant BALB/c mouse. A primary genetic lesion closely linked to defective esterification of exogenously derived cholesterol and its relationship to human type C Niemann-Pick disease. J Biol Chem. 1986;261:2772-7 pubmed
  4. Gadola S, Silk J, Jeans A, Illarionov P, Salio M, Besra G, et al. Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases. J Exp Med. 2006;203:2293-303 pubmed
    ..These data suggest that GSL storage may result in alterations in thymic selection of iNKT cells caused by impaired presentation of selecting ligands. ..
  5. Yang S, Kim S, Byun K, Hutchinson B, Lee B, Michikawa M, et al. NPC1 gene deficiency leads to lack of neural stem cell self-renewal and abnormal differentiation through activation of p38 mitogen-activated protein kinase signaling. Stem Cells. 2006;24:292-8 pubmed
    ..The Niemann-Pick type C1 (NPC1) disease is a neurodegenerative disease caused by a mutation of the NPC1 gene that affects the function of the NPC1 ..
  6. Du X, Kumar J, Ferguson C, Schulz T, Ong Y, Hong W, et al. A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking. J Cell Biol. 2011;192:121-35 pubmed publisher accumulate in the limiting membranes of endosomal compartments in ORP5-depleted cells, whereas depletion of NPC1 or both ORP5 and NPC1 results in luminal accumulation of cholesterol...
  7. Griffin L, Gong W, Verot L, Mellon S. Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nat Med. 2004;10:704-11 pubmed
    ..Earlier administration increases effectiveness of treatment. Decreased production of allopregnanolone apparently contributes to the pathology of NP-C; thus, neurosteroid treatment may be useful in ameliorating progression of the disease...
  8. Amritraj A, Peake K, Kodam A, Salio C, Merighi A, Vance J, et al. Increased activity and altered subcellular distribution of lysosomal enzymes determine neuronal vulnerability in Niemann-Pick type C1-deficient mice. Am J Pathol. 2009;175:2540-56 pubmed publisher
    Niemann-Pick disease type C (NPC), caused by mutations in the Npc1 or Npc2 genes, is a progressive neurodegenerative disorder characterized by intracellular accumulation/redistribution of cholesterol in a number of tissues including the ..
  9. Sawamura N, Gong J, Garver W, Heidenreich R, Ninomiya H, Ohno K, et al. Site-specific phosphorylation of tau accompanied by activation of mitogen-activated protein kinase (MAPK) in brains of Niemann-Pick type C mice. J Biol Chem. 2001;276:10314-9 pubmed
    ..From these results we conclude that abnormal cholesterol metabolism due to the genetic mutation in NPC1 may be responsible for activation of the mitogen-activated protein kinase-signaling pathway and site-specific ..

More Information


  1. Goldman S, Krise J. Niemann-Pick C1 functions independently of Niemann-Pick C2 in the initial stage of retrograde transport of membrane-impermeable lysosomal cargo. J Biol Chem. 2010;285:4983-94 pubmed publisher
    The rare neurodegenerative disease Niemann-Pick Type C (NPC) results from mutations in either NPC1 or NPC2, which are membrane-bound and soluble lysosomal proteins, respectively...
  2. Miyawaki S, Mitsuoka S, Sakiyama T, Kitagawa T. Sphingomyelinosis, a new mutation in the mouse: a model of Niemann-Pick disease in humans. J Hered. 1982;73:257-63 pubmed
    A new autosomal recessive gene causing sphingomyelinosis in mice is described. The name sphingomyelinosis is proposed for this mutant with the gene symbol spm...
  3. Erickson R, Bhattacharyya A, Hunter R, Heidenreich R, Cherrington N. Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet. Am J Physiol Gastrointest Liver Physiol. 2005;289:G300-7 pubmed
    ..b>Npc1-/- mice of both sexes, with or without the Ldlr knockout, were fed a 18% fat, 1% cholesterol ("high-fat") ..
  4. Vázquez M, del Pozo T, Robledo F, Carrasco G, Pavez L, Olivares F, et al. Alteration of gene expression profile in Niemann-Pick type C mice correlates with tissue damage and oxidative stress. PLoS ONE. 2011;6:e28777 pubmed publisher
    ..Here, we assessed hepatic tissue integrity, biochemical and oxidative stress parameters of wild-type control (Npc1(+/+); WT) and homozygous-mutant (Npc1(-/-); NPC) mice...
  5. Shio H, Fowler S, Bhuvaneswaran C, Morris M. Lysosome lipid storage disorder in NCTR-BALB/c mice. II. Morphologic and cytochemical studies. Am J Pathol. 1982;108:150-9 pubmed
    ..Clefts of cholesterol crystals were seen in the inclusions in liver, spleen, and lung. We conclude that the NCTR-BALB/c mice are affected by a lysosome lipid storage disease and that cholesterol is a major storage product. ..
  6. Reid P, Sakashita N, Sugii S, Ohno Iwashita Y, Shimada Y, Hickey W, et al. A novel cholesterol stain reveals early neuronal cholesterol accumulation in the Niemann-Pick type C1 mouse brain. J Lipid Res. 2004;45:582-91 pubmed
    ..In the NPC1 mouse model, neurodegeneration and neuronal cell loss occur before postnatal day 21...
  7. Jelinek D, Heidenreich R, Erickson R, Garver W. Decreased Npc1 gene dosage in mice is associated with weight gain. Obesity (Silver Spring). 2010;18:1457-9 pubmed publisher
    A recent genome-wide association study has determined that the Niemann-Pick C1 (NPC1) gene is associated with early-onset and morbid adult obesity...
  8. Henderson L, Lin L, Prasad A, Paul C, Chang T, Maue R. Embryonic striatal neurons from niemann-pick type C mice exhibit defects in cholesterol metabolism and neurotrophin responsiveness. J Biol Chem. 2000;275:20179-87 pubmed
    ..Moreover, this defect is associated with a lack of TrkB function and BDNF responsiveness, which may contribute to the loss of neuronal function observed in NP-C disease. ..
  9. Morris M, Bhuvaneswaran C, Shio H, Fowler S. Lysosome lipid storage disorder in NCTR-BALB/c mice. I. Description of the disease and genetics. Am J Pathol. 1982;108:140-9 pubmed
    ..Significant increases in phosphatidylcholine occur also in spleen and lung. The disorder is inherited, affecting both sexes equally, and appears to be transmitted as an autosomal recessive mutation. ..
  10. Klein A, Maldonado C, Vargas L, Gonzalez M, Robledo F, Perez de Arce K, et al. Oxidative stress activates the c-Abl/p73 proapoptotic pathway in Niemann-Pick type C neurons. Neurobiol Dis. 2011;41:209-18 pubmed publisher
    ..In conclusion, our data suggest that oxidative stress is the main upstream stimulus activating the c-Abl/p73 pathway and neuronal apoptosis in NPC neurons. ..
  11. Maulik M, Ghoshal B, Kim J, Wang Y, Yang J, Westaway D, et al. Mutant human APP exacerbates pathology in a mouse model of NPC and its reversal by a ?-cyclodextrin. Hum Mol Genet. 2012;21:4857-75 pubmed publisher
    Niemann-Pick type C (NPC) disease, an autosomal recessive disorder caused primarily by loss-of-function mutations in NPC1 gene, is characterized neuropathologically by intracellular cholesterol accumulation, gliosis and neuronal loss in ..
  12. Hovakimyan M, Petersen J, Maass F, Reichard M, Witt M, Lukas J, et al. Corneal alterations during combined therapy with cyclodextrin/allopregnanolone and miglustat in a knock-out mouse model of NPC1 disease. PLoS ONE. 2011;6:e28418 pubmed publisher
    Niemann Pick disease type C1 is a neurodegenerative disease caused by mutations in the NPC1 gene, which result in accumulation of unesterified cholesterol and glycosphingolipids in the endosomal-lysosomal system as well as limiting ..
  13. Zhang J, Coleman T, Langmade S, Scherrer D, Lane L, Lanier M, et al. Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking. J Clin Invest. 2008;118:2281-90 pubmed publisher
    Niemann-Pick C1 (NPC1) is a key participant in cellular cholesterol trafficking...
  14. Zervas M, Somers K, Thrall M, Walkley S. Critical role for glycosphingolipids in Niemann-Pick disease type C. Curr Biol. 2001;11:1283-7 pubmed
    Niemann-Pick type C (NPC) disease is a cholesterol lipidosis caused by mutations in NPC1 and NPC2 gene loci. Most human cases are caused by defects in NPC1, as are the spontaneously occurring NPC diseases in mice and cats...
  15. Ohara S, Ukita Y, Ninomiya H, Ohno K. Axonal dystrophy of dorsal root ganglion sensory neurons in a mouse model of Niemann-Pick disease type C. Exp Neurol. 2004;187:289-98 pubmed
    ..A Balb/c-npc1 mutant strain is a genetically authentic murine model of NP-C, and homozygous mice show progressive weight loss and ..
  16. Liao G, Wen Z, Irizarry K, Huang Y, Mitsouras K, Darmani M, et al. Abnormal gene expression in cerebellum of Npc1-/- mice during postnatal development. Brain Res. 2010;1325:128-40 pubmed publisher
    ..Genetic analyses have identified mutations in NPC1 gene in the great majority of cases, while mutations in NPC2 account for the remainders...
  17. Zhang M, Strnatka D, Donohue C, Hallows J, Vincent I, Erickson R. Astrocyte-only Npc1 reduces neuronal cholesterol and triples life span of Npc1-/- mice. J Neurosci Res. 2008;86:2848-56 pubmed publisher
    ..Although neurodegeneration of Purkinje cells in the mouse model (Npc1(-/-)) is thought to be autonomous, the basis of neuronal death in other regions of the brain remains elusive...
  18. Pacheco C, Kunkel R, Lieberman A. Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects. Hum Mol Genet. 2007;16:1495-503 pubmed
    ..Most cases are caused by loss of function mutations in the Npc1 gene, which encodes a protein that localizes to late endosomes and functions in lipid sorting and vesicle ..
  19. Suzuki M, Sugimoto Y, Ohsaki Y, Ueno M, Kato S, Kitamura Y, et al. Endosomal accumulation of Toll-like receptor 4 causes constitutive secretion of cytokines and activation of signal transducers and activators of transcription in Niemann-Pick disease type C (NPC) fibroblasts: a potential basis for glial cell activati. J Neurosci. 2007;27:1879-91 pubmed
    Niemann-Pick disease type C (NPC) is an inherited lipid storage disorder caused by mutations in NPC1 or NPC2 genes...
  20. Bhuvaneswaran C, Morris M, Shio H, Fowler S. Lysosome lipid storage disorder in NCTR-BALB/c mice. III. Isolation and analysis of storage inclusions from liver. Am J Pathol. 1982;108:160-70 pubmed
    ..We propose several possible mechanisms to explain the cholesterol and phospholipid overloading of lysosomes. The specific gene defect remains to be established. ..
  21. Morales M, Amigo L, Balboa E, Acuña M, Castro J, Molina H, et al. Deficiency of Niemann-Pick C1 protein protects against diet-induced gallstone formation in mice. Liver Int. 2010;30:887-97 pubmed publisher
    ..Because Niemann-Pick C1 (NPC1) protein is a key component for the intracellular distribution of cholesterol originating from lipoprotein ..
  22. Nunes A, Pressey S, Cooper J, Soriano S. Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis. Neurobiol Dis. 2011;42:349-59 pubmed publisher
  23. Aqul A, Liu B, Ramirez C, Pieper A, Estill S, Burns D, et al. Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment. J Neurosci. 2011;31:9404-13 pubmed publisher
    ..requires processing that involves two lysosomal proteins, lysosomal acid lipase, which hydrolyzes C esters, and NPC1 (Niemann-Pick type C1)...
  24. Pentchev P, Boothe A, Kruth H, Weintroub H, Stivers J, Brady R. A genetic storage disorder in BALB/C mice with a metabolic block in esterification of exogenous cholesterol. J Biol Chem. 1984;259:5784-91 pubmed
    ..The attenuation in tissue levels of sphingomyelinase and glucocerebrosidase and the accumulation of sphingolipids may reflect alterations in lysosomal function resulting from an imbalance of unesterified cholesterol in these organelles. ..
  25. Baudry M, Yao Y, Simmons D, Liu J, Bi X. Postnatal development of inflammation in a murine model of Niemann-Pick type C disease: immunohistochemical observations of microglia and astroglia. Exp Neurol. 2003;184:887-903 pubmed
    ..In most cases, NPC is caused by mutations of the NPC1 gene, which encodes a glycoprotein playing an important role in cholesterol transport...
  26. Repa J, Li H, Frank Cannon T, Valasek M, Turley S, TANSEY M, et al. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J Neurosci. 2007;27:14470-80 pubmed
    ..In Niemann-Pick type C (NPC) disease, a mutation in NPC1 protein causes unesterified cholesterol to accumulate in the lysosomal compartment of every cell, including neurons ..
  27. Lloyd Evans E, Morgan A, He X, Smith D, Elliot Smith E, Sillence D, et al. Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med. 2008;14:1247-55 pubmed publisher
    Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder caused by mutations in the acidic compartment (which we define as the late endosome and the lysosome) protein, NPC1...
  28. Claudepierre T, Paques M, Simonutti M, Buard I, Sahel J, Maue R, et al. Lack of Niemann-Pick type C1 induces age-related degeneration in the mouse retina. Mol Cell Neurosci. 2010;43:164-76 pubmed publisher
    Niemann-Pick type C (NPC) disease is an inherited lysosomal storage disease and caused by mutations in Npc1 or Npc2, which mediate cooperatively the egress of cholesterol from lysosomes...
  29. Patel S, Suresh S, Kumar U, Hu C, Cooney A, Blanchette Mackie E, et al. Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann- Pick type C disease. Proc Natl Acad Sci U S A. 1999;96:1657-62 pubmed
    ..Most cases of NP-C result from inactivating mutations of NPC1, a recently identified member of a family of genes encoding membrane-bound proteins containing putative sterol ..
  30. Liu B, Li H, Repa J, Turley S, Dietschy J. Genetic variations and treatments that affect the lifespan of the NPC1 mouse. J Lipid Res. 2008;49:663-9 pubmed
    Niemann-Pick type C (NPC) disease is a multisystem disorder caused primarily by a mutation in the npc1 gene...
  31. Gelsthorpe M, Baumann N, Millard E, Gale S, Langmade S, Schaffer J, et al. Niemann-Pick type C1 I1061T mutant encodes a functional protein that is selected for endoplasmic reticulum-associated degradation due to protein misfolding. J Biol Chem. 2008;283:8229-36 pubmed publisher
    Over 200 disease-causing mutations have been identified in the NPC1 gene...
  32. Liao G, Yao Y, Liu J, Yu Z, Cheung S, Xie A, et al. Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in Npc1 -/- mouse brain. Am J Pathol. 2007;171:962-75 pubmed
    Niemann-Pick type C (NPC) disease is an autosomal recessive disorder caused by mutations of NPC1 and NPC2 genes. Progressive neurodegeneration that accompanies NPC is fatal, but the underlying mechanisms are still poorly understood...
  33. Karten B, Campenot R, Vance D, Vance J. The Niemann-Pick C1 protein in recycling endosomes of presynaptic nerve terminals. J Lipid Res. 2006;47:504-14 pubmed
    ..type C (NPC) disease is a fatal, neurodegenerative disorder caused in 95% of cases by loss of function of NPC1, a ubiquitous endosomal transmembrane protein...
  34. Yu T, Lieberman A. Npc1 acting in neurons and glia is essential for the formation and maintenance of CNS myelin. PLoS Genet. 2013;9:e1003462 pubmed publisher
    ..To address this question, we used mice with a conditional null allele of the Npc1 gene, which encodes a transmembrane protein critical for mobilizing cholesterol from the endolysosomal system...
  35. German D, Quintero E, Liang C, Xie C, Dietschy J. Degeneration of neurons and glia in the Niemann-Pick C mouse is unrelated to the low-density lipoprotein receptor. Neuroscience. 2001;105:999-1005 pubmed
  36. Burns M, Gaynor K, Olm V, Mercken M, LaFrancois J, Wang L, et al. Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo. J Neurosci. 2003;23:5645-9 pubmed
    ..Our results show that aberrant cholesterol trafficking is associated with the potentiation of APP processing components in vivo, leading to an overall increase in Abeta levels...
  37. Prasad A, Fischer W, Maue R, Henderson L. Regional and developmental expression of the Npc1 mRNA in the mouse brain. J Neurochem. 2000;75:1250-7 pubmed
    ..Recently, a gene mutated in NP-C disease (NPC1) was identified in both human patients and in the npc(nih) mouse model...
  38. Charman M, Kennedy B, Osborne N, Karten B. MLN64 mediates egress of cholesterol from endosomes to mitochondria in the absence of functional Niemann-Pick Type C1 protein. J Lipid Res. 2010;51:1023-34 pubmed publisher
    ..disease is a fatal, neurodegenerative disorder, caused in most cases by mutations in the late endosomal protein NPC1. A hallmark of NPC disease is endosomal cholesterol accumulation and an impaired cholesterol homeostatic response, ..
  39. Karten B, Hayashi H, Francis G, Campenot R, Vance D, Vance J. Generation and function of astroglial lipoproteins from Niemann-Pick type C1-deficient mice. Biochem J. 2005;387:779-88 pubmed
    ..Although these alterations appear to occur in all NPC1-deficient cell types, the consequences are most profound in the nervous system...
  40. Sarna J, Larouche M, Marzban H, Sillitoe R, Rancourt D, Hawkes R. Patterned Purkinje cell degeneration in mouse models of Niemann-Pick type C disease. J Comp Neurol. 2003;456:279-91 pubmed
    Niemann Pick disease type C1 (NPC1) is an inherited, autosomal recessive, lipid-storage disorder with major neurological involvement. Purkinje cell death is a prominent feature of the neuropathology of NPC...
  41. Yu T, Shakkottai V, Chung C, Lieberman A. Temporal and cell-specific deletion establishes that neuronal Npc1 deficiency is sufficient to mediate neurodegeneration. Hum Mol Genet. 2011;20:4440-51 pubmed publisher
    Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in the NPC1 or NPC2 genes...
  42. Alvarez A, Klein A, Castro J, Cancino G, Amigo J, Mosqueira M, et al. Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease. FASEB J. 2008;22:3617-27 pubmed publisher
    ..We used the NPC1 mouse model to evaluate c-Abl/p73 expression and activation in the cerebellum and the effect of therapy with the c-..
  43. Elrick M, Yu T, Chung C, Lieberman A. Impaired proteolysis underlies autophagic dysfunction in Niemann-Pick type C disease. Hum Mol Genet. 2012;21:4876-87 pubmed publisher a childhood onset neurodegenerative disorder arising from lipid-trafficking defects caused by mutations in the NPC1 or NPC2 gene...
  44. Xu S, Zhou S, Xia D, Xia J, Chen G, Duan S, et al. Defects of synaptic vesicle turnover at excitatory and inhibitory synapses in Niemann-Pick C1-deficient neurons. Neuroscience. 2010;167:608-20 pubmed publisher
    ..and fluorescent dye studies were applied to examine neuron-specific functions of Niemann-Pick disease type C1 (NPC1) and to determine whether excitatory and inhibitory synapses are differentially impaired by NPC1 deficiency...
  45. Klein A, Amigo L, Retamal M, Morales M, Miquel J, Rigotti A, et al. NPC2 is expressed in human and murine liver and secreted into bile: potential implications for body cholesterol homeostasis. Hepatology. 2006;43:126-33 pubmed
    ..In addition, hepatic NPC2 protein expression was dramatically increased in NPC1-deficient mice but not regulated by cholesterol feeding or pharmacological modulation of various nuclear receptors ..
  46. Otterbach B, Stoffel W. Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick disease). Cell. 1995;81:1053-61 pubmed
    ..Furthermore, it provides a suitable model for the development of strategies for somatic gene therapy. ..
  47. Ko D, Milenkovic L, BEIER S, Manuel H, Buchanan J, Scott M. Cell-autonomous death of cerebellar purkinje neurons with autophagy in Niemann-Pick type C disease. PLoS Genet. 2005;1:81-95 pubmed
    Niemann-Pick type C is a neurodegenerative lysosomal storage disorder caused by mutations in either of two genes, npc1 and npc2...
  48. Lopez M, Klein A, Dimbil U, Scott M. Anatomically defined neuron-based rescue of neurodegenerative Niemann-Pick type C disorder. J Neurosci. 2011;31:4367-78 pubmed publisher
    Niemann-Pick type C disease is a fatal lysosomal storage disorder caused by loss of NPC1 function. The disorder severely affects multiple body systems, particularly the nervous system...
  49. Ong Q, Lim M, Chua C, Cheung N, Wong B. Impaired insulin signaling in an animal model of Niemann-Pick Type C disease. Biochem Biophys Res Commun. 2012;424:482-7 pubmed publisher
    ..To our knowledge, this is the first report documenting impaired insulin signaling in the brain of a NPC mouse model. ..
  50. Xu S, Chen X, Wei X, Liu G, Wang Q. Presynaptic impairment in Niemann-Pick C1-deficient neurons: not dependent on presence of glial cells. Neurosci Lett. 2011;496:54-9 pubmed publisher
    ..Furthermore, we would like to ascertain whether such defects are caused by direct effect of NPC1 deficiency in neurons or indirect effect of NPC1 deficiency in glial cells...
  51. Wu Y, Mizukami H, Matsuda J, Saito Y, Proia R, Suzuki K. Apoptosis accompanied by up-regulation of TNF-alpha death pathway genes in the brain of Niemann-Pick type C disease. Mol Genet Metab. 2005;84:9-17 pubmed
    ..Collectively, our results suggest that the cell death in the brain of NP-C disease occurs through apoptosis and it is mediated by the TNF receptor superfamily pathway. ..
  52. Loftus S, Erickson R, Walkley S, Bryant M, Incao A, Heidenreich R, et al. Rescue of neurodegeneration in Niemann-Pick C mice by a prion-promoter-driven Npc1 cDNA transgene. Hum Mol Genet. 2002;11:3107-14 pubmed
    ..extent to which visceral disease contributes to neurodegeneration by making transgenic mice in which the wild-type NPC1 protein is expressed primarily in the CNS using the prion promoter...
  53. Ohsaki Y, Sugimoto Y, Suzuki M, Hosokawa H, Yoshimori T, Davies J, et al. Cholesterol depletion facilitates ubiquitylation of NPC1 and its association with SKD1/Vps4. J Cell Sci. 2006;119:2643-53 pubmed
    Niemann-Pick disease type C (NPC) is an inherited lipid storage disorder caused by mutations in NPC1 or NPC2...
  54. Pentchev P, Gal A, Booth A, Omodeo Salè F, Fouks J, Neumeyer B, et al. A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase. Biochim Biophys Acta. 1980;619:669-79 pubmed
    ..Heterozygous mice were biochemically indistinguishable from normal controls. The phenotypic manifestations in these metabolically mutated animals are compared with those in Niemann-Pick disease and Gaucher's disease in humans. ..
  55. te Vruchte D, Lloyd Evans E, Veldman R, Neville D, Dwek R, Platt F, et al. Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport. J Biol Chem. 2004;279:26167-75 pubmed
    ..High pressure liquid chromatography and mass spectrometric analysis of NPC1(-/-) mouse brain revealed large increases in GSL...
  56. Dixit S, Sleat D, Stock A, Lobel P. Do mammalian NPC1 and NPC2 play a role in intestinal cholesterol absorption?. Biochem J. 2007;408:1-5 pubmed
    ..Two proteins that might be involved in this process are NPC1 and NPC2 (Niemann-Pick disease type C proteins 1 and 2), which function in the endosomal/lysosomal cholesterol ..
  57. Xie C, Turley S, Dietschy J. Cholesterol accumulation in tissues of the Niemann-pick type C mouse is determined by the rate of lipoprotein-cholesterol uptake through the coated-pit pathway in each organ. Proc Natl Acad Sci U S A. 1999;96:11992-7 pubmed
  58. Hawes C, Wiemer H, Krueger S, Karten B. Pre-synaptic defects of NPC1-deficient hippocampal neurons are not directly related to plasma membrane cholesterol. J Neurochem. 2010;114:311-22 pubmed publisher
    ..In Niemann-Pick Type C (NPC) disease, mutations in NPC1 or NPC2 lead to endosomal cholesterol accumulation, neuronal dysfunction and death...
  59. Takikita S, Fukuda T, Mohri I, Yagi T, Suzuki K. Perturbed myelination process of premyelinating oligodendrocyte in Niemann-Pick type C mouse. J Neuropathol Exp Neurol. 2004;63:660-73 pubmed
  60. Parra J, Klein A, Castro J, Morales M, Mosqueira M, Valencia I, et al. Npc1 deficiency in the C57BL/6J genetic background enhances Niemann-Pick disease type C spleen pathology. Biochem Biophys Res Commun. 2011;413:400-6 pubmed publisher
    ..The affected genes are NPC1 and NPC2. Mutations in either gene lead to intracellular cholesterol accumulation...
  61. Jelinek D, Millward V, Birdi A, Trouard T, Heidenreich R, Garver W. Npc1 haploinsufficiency promotes weight gain and metabolic features associated with insulin resistance. Hum Mol Genet. 2011;20:312-21 pubmed publisher
    A recent population-based genome-wide association study has revealed that the Niemann-Pick C1 (NPC1) gene is associated with early-onset and morbid adult obesity...
  62. Sagiv Y, Hudspeth K, Mattner J, Schrantz N, Stern R, Zhou D, et al. Cutting edge: impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein. J Immunol. 2006;177:26-30 pubmed
    Niemann-Pick type C1 (NPC1) is a late endosomal/lysosomal transmembrane protein involved in the cellular transport of glycosphingolipids and cholesterol that is mutated in a majority of patients with Niemann-Pick C neurodegenerative ..
  63. Mari M, Caballero F, Colell A, Morales A, Caballeria J, Fernandez A, et al. Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab. 2006;4:185-98 pubmed
    ..Moreover, hepatocytes from mice lacking NPC1, a late endosomal cholesterol trafficking protein, or from obese ob/ob mice, exhibited mitochondrial FC ..
  64. Lopez M, Klein A, Hong J, Dimbil U, Scott M. Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C. Hum Mol Genet. 2012;21:2946-60 pubmed publisher
    ..Without further exploration of possible beneficial roles of inflammatory mediators, targeting inflammation may not be therapeutically effective at ameliorating disease severity. ..
  65. Ulatowski L, Parker R, Davidson C, Yanjanin N, Kelley T, Corey D, et al. Altered vitamin E status in Niemann-Pick type C disease. J Lipid Res. 2011;52:1400-10 pubmed publisher
    ..Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene, which regulates lipid transport through the endocytic pathway...
  66. Jelinek D, Castillo J, Garver W. The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage has impaired glucose tolerance independent of body weight. Gene. 2013;527:65-70 pubmed publisher
    The human Niemann-Pick C1 (NPC1) gene has been found to be associated with extreme (early-onset and morbid-adult) obesity and type 2 diabetes independent of body weight...
  67. Liao G, Cheung S, Galeano J, Ji A, Qin Q, Bi X. Allopregnanolone treatment delays cholesterol accumulation and reduces autophagic/lysosomal dysfunction and inflammation in Npc1-/- mouse brain. Brain Res. 2009;1270:140-51 pubmed publisher
    ..that a single injection of the neurosteroid allopregnanolone at postnatal day 7 significantly prolonged lifespan of Npc1-/- mice. However, the cellular/molecular basis for this beneficial effect remains undefined...
  68. Chen G, Li H, Chen Y, Gu X, Duan S. Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann-Pick disease type C. Glia. 2007;55:1509-18 pubmed
    Niemann-Pick disease type C (NPC) is a deadly neurodegenerative disease often caused by mutation in a gene called NPC1, which results in the accumulation of unesterified cholesterol and glycosphingolipids in the endosomal-lysosomal system...
  69. Elrick M, Pacheco C, Yu T, Dadgar N, Shakkottai V, Ware C, et al. Conditional Niemann-Pick C mice demonstrate cell autonomous Purkinje cell neurodegeneration. Hum Mol Genet. 2010;19:837-47 pubmed publisher
    ..Using gene targeting, we generate Npc1 conditional null mutant mice...
  70. Mutka A, Lusa S, Linder M, Jokitalo E, Kopra O, Jauhiainen M, et al. Secretion of sterols and the NPC2 protein from primary astrocytes. J Biol Chem. 2004;279:48654-62 pubmed
    ..Astrocytes derived from Niemann-Pick type C lipidosis (NPC1-/-) mice displayed late endosomal cholesterol deposits, but the secretion of biosynthetic sterols from the cells ..
  71. Sleat D, Wiseman J, El Banna M, Price S, Verot L, Shen M, et al. Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc Natl Acad Sci U S A. 2004;101:5886-91 pubmed
    ..Clinically identical forms of NPC disease are caused by defects in either of two different proteins: NPC1, a lysosomal-endosomal transmembrane protein and NPC2, a soluble lysosomal protein with cholesterol binding ..
  72. Karten B, Vance D, Campenot R, Vance J. Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons. J Neurochem. 2002;83:1154-63 pubmed
    ..Unlike other tissues, however, NPC1-deficient brains do not accumulate cholesterol but whether or not NPC1-deficient neurons accumulate cholesterol is ..
  73. Weintraub H, Abramovici A, Sandbank U, Pentchev P, Brady R, Sekine M, et al. Neurological mutation characterized by dysmyelination in NCTR-Balb/C mouse with lysosomal lipid storage disease. J Neurochem. 1985;45:665-72 pubmed
  74. Muralidhar A, Borbon I, Esharif D, Ke W, Manacheril R, DAINES M, et al. Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1?/? mice. Mol Genet Metab. 2011;103:142-7 pubmed publisher
    Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1(NIH/NIH) mouse model...
  75. Bi X, Liao G. Autophagic-lysosomal dysfunction and neurodegeneration in Niemann-Pick Type C mice: lipid starvation or indigestion?. Autophagy. 2007;3:646-8 pubmed
    ..About 95% of the cases are caused by mutations in the NPC1 gene, whereas the remaining 5% are due to mutations in the NPC2 gene...
  76. Deffieu M, Pfeffer S. Niemann-Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding. Proc Natl Acad Sci U S A. 2011;108:18932-6 pubmed publisher
    Niemann-Pick type C1 (NPC1) protein is needed for cellular utilization of low-density lipoprotein-derived cholesterol that has been delivered to lysosomes...
  77. German D, Liang C, Song T, Yazdani U, Xie C, Dietschy J. Neurodegeneration in the Niemann-Pick C mouse: glial involvement. Neuroscience. 2002;109:437-50 pubmed
    ..The activation of astrocytes in regions that undergo neurodegeneration is also consistent with a role for these glial cells in the neurodegenerative process. ..
  78. Horinouchi K, Erlich S, Perl D, Ferlinz K, Bisgaier C, Sandhoff K, et al. Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease. Nat Genet. 1995;10:288-93 pubmed
    ..Thus, the ASM deficient mice should be of great value for studying the pathogenesis and treatment of NPD, and for investigations into the role of ASM in signal transduction and apoptosis. ..
  79. Liu B, Turley S, Burns D, Miller A, Repa J, Dietschy J. Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse. Proc Natl Acad Sci U S A. 2009;106:2377-82 pubmed publisher
    Niemann-Pick type C disease is largely attributable to an inactivating mutation of NPC1 protein, which normally aids movement of unesterified cholesterol (C) from the endosomal/lysosomal (E/L) compartment to the cytosolic compartment of ..
  80. Chen F, Gordon R, Ioannou Y. NPC1 late endosomes contain elevated levels of non-esterified ('free') fatty acids and an abnormally glycosylated form of the NPC2 protein. Biochem J. 2005;390:549-61 pubmed
    ..To investigate the relationship between NPC1 and NPC2 and their potential role in NPC disease pathogenesis, we have developed a method for the rapid and ..
  81. Amigo L, Mendoza H, Castro J, Quinones V, Miquel J, Zanlungo S. Relevance of Niemann-Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice. Hepatology. 2002;36:819-28 pubmed
    ..Because Niemann-Pick C1 (NPC1) protein is a key component in the intracellular distribution of cholesterol obtained from lipoproteins by the ..