{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:08:57Z","timestamp":1762898937180,"version":"3.41.2"},"reference-count":99,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":3059,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Understanding neurodegenerative disease progression and its treatment requires the systematic characterization and manipulation of relevant cell types and molecular pathways. The neurodegenerative lysosomal storage disorder Niemann-Pick disease type C (NPC) is highly amenable to genetic approaches that allow exploration of the disease biology at the organismal, cellular and molecular level. Although NPC is a rare disease, genetic analysis of the associated neuropathology promises to provide insight into the logic of disease neural circuitry, selective neuron vulnerability and neural-glial interactions. The ability to control the disorder cell-autonomously and in naturally occurring spontaneous animal models that recapitulate many aspects of the human disease allows for an unparalleled dissection of the disease neurobiology in vivo. Here, we review progress in mouse-model-based studies of NPC disease, specifically focusing on the subtype that is caused by a deficiency in NPC1, a sterol-binding late endosomal membrane protein involved in lipid trafficking. We also discuss recent findings and future directions in NPC disease research that are pertinent to understanding the cellular and molecular mechanisms underlying neurodegeneration in general.<\/jats:p>","DOI":"10.1242\/dmm.012385","type":"journal-article","created":{"date-parts":[[2013,8,2]],"date-time":"2013-08-02T05:01:06Z","timestamp":1375419666000},"source":"Crossref","is-referenced-by-count":12,"title":["Genetic dissection of a cell-autonomous neurodegenerative disorder: lessons learned from mouse models of Niemann-Pick disease type C"],"prefix":"10.1242","author":[{"given":"Manuel E.","family":"Lopez","sequence":"first","affiliation":[{"name":"Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew P.","family":"Scott","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2021042501151019400_b1-0061089","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature11057","article-title":"Brain-wide neuronal dynamics during motor adaptation in zebrafish","volume":"485","author":"Ahrens","year":"2012","journal-title":"Nature"},{"key":"2021042501151019400_b2-0061089","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/sj.cdd.4402013","article-title":"Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway","volume":"14","author":"Bifsha","year":"2007","journal-title":"Cell Death Differ."},{"key":"2021042501151019400_b3-0061089","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/hmg\/ddg025","article-title":"Defective endocytic trafficking of NPC1 and NPC2 underlying infantile Niemann-Pick type C disease","volume":"12","author":"Blom","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"2021042501151019400_b4-0061089","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3233\/JAD-2012-120199","article-title":"Niemann-Pick C1 mice, a model of \u2018juvenile Alzheimer\u2019s disease\u2019, with normal gene expression in neurons and fibrillary astrocytes show long term survival and delayed neurodegeneration","volume":"30","author":"Borbon","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"2021042501151019400_b5-0061089","doi-asserted-by":"crossref","first-page":"e49015","DOI":"10.1371\/journal.pone.0049015","article-title":"Purkinje cell maturation participates in the control of oligodendrocyte differentiation: role of sonic hedgehog and vitronectin","volume":"7","author":"Bouslama-Oueghlani","year":"2012","journal-title":"PLoS ONE"},{"key":"2021042501151019400_b6-0061089","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1093\/hmg\/dds089","article-title":"Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis","volume":"21","author":"Bras","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2021042501151019400_b7-0061089","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.fgb.2011.03.001","article-title":"Npc1 is involved in sterol trafficking in the filamentous fungus Fusarium graminearum","volume":"48","author":"Breakspear","year":"2011","journal-title":"Fungal Genet. Biol."},{"key":"2021042501151019400_b8-0061089","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nature10348","article-title":"Ebola virus entry requires the cholesterol transporter Niemann-Pick C1","volume":"477","author":"Carette","year":"2011","journal-title":"Nature"},{"key":"2021042501151019400_b9-0061089","doi-asserted-by":"crossref","first-page":"31594","DOI":"10.1016\/S0021-9258(19)84073-5","article-title":"Mechanism of cholesterol transfer from the Niemann-Pick type C2 protein to model membranes supports a role in lysosomal cholesterol transport","volume":"281","author":"Cheruku","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2021042501151019400_b10-0061089","doi-asserted-by":"crossref","first-page":"e47845","DOI":"10.1371\/journal.pone.0047845","article-title":"Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight","volume":"7","author":"Cologna","year":"2012","journal-title":"PLoS ONE"},{"key":"2021042501151019400_b11-0061089","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nature10380","article-title":"Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection","volume":"477","author":"C\u00f4t\u00e9","year":"2011","journal-title":"Nature"},{"key":"2021042501151019400_b12-0061089","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/nn1750","article-title":"Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport","volume":"9","author":"Custer","year":"2006","journal-title":"Nat. Neurosci."},{"key":"2021042501151019400_b13-0061089","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1242\/dev.126.14.3089","article-title":"Sonic hedgehog regulates the growth and patterning of the cerebellum","volume":"126","author":"Dahmane","year":"1999","journal-title":"Development"},{"key":"2021042501151019400_b14-0061089","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1126\/science.1069883","article-title":"A genomic regulatory network for development","volume":"295","author":"Davidson","year":"2002","journal-title":"Science"},{"key":"2021042501151019400_b15-0061089","doi-asserted-by":"crossref","first-page":"18932","DOI":"10.1073\/pnas.1110439108","article-title":"Niemann-Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding","volume":"108","author":"Deffieu","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042501151019400_b16-0061089","doi-asserted-by":"crossref","first-page":"9611","DOI":"10.1073\/pnas.1112368109","article-title":"Loss of P-type ATPase ATP13A2\/PARK9 function induces general lysosomal deficiency and leads to Parkinson disease neurodegeneration","volume":"109","author":"Dehay","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042501151019400_b17-0061089","doi-asserted-by":"crossref","first-page":"W465","DOI":"10.1093\/nar\/gkn180","article-title":"Phylogeny.fr: robust phylogenetic analysis for the non-specialist","volume":"36","author":"Dereeper","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2021042501151019400_b18-0061089","doi-asserted-by":"crossref","first-page":"E2334","DOI":"10.1073\/pnas.1209577109","article-title":"Astrocyte dysfunction triggers neurodegeneration in a lysosomal storage disorder","volume":"109","author":"Di Malta","year":"2012","journal-title":"Proc. Natl. Acad. Sci. 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Mech."},{"key":"2021042501151019400_b22-0061089","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1534\/genetics.105.046565","article-title":"Mutations of a Drosophila NPC1 gene confer sterol and ecdysone metabolic defects","volume":"172","author":"Fluegel","year":"2006","journal-title":"Genetics"},{"key":"2021042501151019400_b23-0061089","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1212\/WNL.0b013e31828f180e","article-title":"The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease","volume":"80","author":"Gan-Or","year":"2013","journal-title":"Neurology"},{"key":"2021042501151019400_b24-0061089","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1161\/ATVBAHA.108.179564","article-title":"The LDL receptor","volume":"29","author":"Goldstein","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021042501151019400_b25-0061089","article-title":"Animal models of lysosomal storage diseases: their development and clinical relevance","volume-title":"Fabry Disease: Perspectives from 5 Years of FOS","author":"Haskins","year":"2006"},{"key":"2021042501151019400_b26-0061089","doi-asserted-by":"crossref","first-page":"e1000146","DOI":"10.1371\/journal.pbio.1000146","article-title":"The hedgehog signaling pathway: where did it come from?","volume":"7","author":"Hausmann","year":"2009","journal-title":"PLoS Biol."},{"key":"2021042501151019400_b27-0061089","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/sj.bmt.1701826","article-title":"Niemann-Pick disease type C (a cellular cholesterol lipidosis) treated by bone marrow transplantation","volume":"24","author":"Hsu","year":"1999","journal-title":"Bone Marrow Transplant."},{"key":"2021042501151019400_b28-0061089","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1242\/dev.02079","article-title":"A Drosophila model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis","volume":"132","author":"Huang","year":"2005","journal-title":"Development"},{"key":"2021042501151019400_b29-0061089","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1172\/JCI44867","article-title":"Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice","volume":"121","author":"Igaz","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2021042501151019400_b30-0061089","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1083\/jcb.200908164","article-title":"Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond","volume":"187","author":"Ilieva","year":"2009","journal-title":"J. Cell Biol."},{"key":"2021042501151019400_b31-0061089","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1074\/jbc.M707943200","article-title":"Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino acid membrane protein","volume":"283","author":"Infante","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2021042501151019400_b32-0061089","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1212\/WNL.0b013e3182088310","article-title":"Niemann-Pick C disease: not your average lysosomal storage disease","volume":"76","author":"Kaye","year":"2011","journal-title":"Neurology"},{"key":"2021042501151019400_b33-0061089","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1091\/mbc.12.3.601","article-title":"Dynamic movements of organelles containing Niemann-Pick C1 protein: NPC1 involvement in late endocytic events","volume":"12","author":"Ko","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"2021042501151019400_b34-0061089","first-page":"81","article-title":"Cell-autonomous death of cerebellar purkinje neurons with autophagy in Niemann-Pick type C disease","volume":"1","author":"Ko","year":"2005","journal-title":"PLoS Genet."},{"key":"2021042501151019400_b35-0061089","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.3390\/v4112471","article-title":"Niemann-Pick C1 (NPC1)\/NPC1-like1 chimeras define sequences critical for NPC1\u2019s function as a flovirus entry receptor","volume":"4","author":"Krishnan","year":"2012","journal-title":"Viruses"},{"key":"2021042501151019400_b36-0061089","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1074\/jbc.M610001200","article-title":"Lipid homeostasis and lipoprotein secretion in Niemann-Pick C1-deficient hepatocytes","volume":"282","author":"Kulinski","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2021042501151019400_b37-0061089","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature04657","article-title":"A small-molecule screen in C. elegans yields a new calcium channel antagonist","volume":"441","author":"Kwok","year":"2006","journal-title":"Nature"},{"key":"2021042501151019400_b38-0061089","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.cell.2009.03.049","article-title":"Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol","volume":"137","author":"Kwon","year":"2009","journal-title":"Cell"},{"key":"2021042501151019400_b39-0061089","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S0896-6273(02)00696-7","article-title":"Disruption of dynein\/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration","volume":"34","author":"LaMonte","year":"2002","journal-title":"Neuron"},{"key":"2021042501151019400_b40-0061089","doi-asserted-by":"crossref","first-page":"5741","DOI":"10.1242\/dev.01408","article-title":"NCR-1 and NCR-2, the C. elegans homologs of the human Niemann-Pick type C1 disease protein, function upstream of DAF-9 in the dauer formation pathways","volume":"131","author":"Li","year":"2004","journal-title":"Development"},{"key":"2021042501151019400_b41-0061089","doi-asserted-by":"crossref","first-page":"962","DOI":"10.2353\/ajpath.2007.070052","article-title":"Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in Npc1 \u2212\/\u2212 mouse brain","volume":"171","author":"Liao","year":"2007","journal-title":"Am. J. Pathol."},{"key":"2021042501151019400_b42-0061089","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.brainres.2010.02.019","article-title":"Abnormal gene expression in cerebellum of Npc1\u2212\/\u2212 mice during postnatal development","volume":"1325","author":"Liao","year":"2010","journal-title":"Brain Res."},{"key":"2021042501151019400_b43-0061089","doi-asserted-by":"crossref","first-page":"e1002410","DOI":"10.1371\/journal.ppat.1002410","article-title":"Deficiency of a Niemann-Pick, type C1-related protein in toxoplasma is associated with multiple lipidoses and increased pathogenicity","volume":"7","author":"Lige","year":"2011","journal-title":"PLoS Pathog."},{"key":"2021042501151019400_b44-0061089","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1194\/jlr.M700525-JLR200","article-title":"Genetic variations and treatments that affect the lifespan of the NPC1 mouse","volume":"49","author":"Liu","year":"2008","journal-title":"J. Lipid Res."},{"key":"2021042501151019400_b45-0061089","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1038\/nm.1876","article-title":"Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium","volume":"14","author":"Lloyd-Evans","year":"2008","journal-title":"Nat. Med."},{"key":"2021042501151019400_b46-0061089","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1126\/science.277.5323.232","article-title":"Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene","volume":"277","author":"Loftus","year":"1997","journal-title":"Science"},{"key":"2021042501151019400_b47-0061089","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1093\/hmg\/11.24.3107","article-title":"Rescue of neurodegeneration in Niemann-Pick C mice by a prion-promoter-driven Npc1 cDNA transgene","volume":"11","author":"Loftus","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"2021042501151019400_b48-0061089","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/jnnp.2006.104828","article-title":"Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues","volume":"79","author":"Logroscino","year":"2008","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"2021042501151019400_b49-0061089","doi-asserted-by":"crossref","first-page":"4367","DOI":"10.1523\/JNEUROSCI.5981-10.2011","article-title":"Anatomically defined neuron-based rescue of neurodegenerative Niemann-Pick type C disorder","volume":"31","author":"Lopez","year":"2011","journal-title":"J. Neurosci."},{"key":"2021042501151019400_b50-0061089","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/1742-2094-9-216","article-title":"Complement is dispensable for neurodegeneration in Niemann-Pick disease type C","volume":"9","author":"Lopez","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"2021042501151019400_b51-0061089","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1093\/hmg\/dds126","article-title":"Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C","volume":"21","author":"Lopez","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2021042501151019400_b52-0061089","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/hmg\/dds401","article-title":"NPC1 defect results in abnormal platelet formation and function: studies in Niemann-Pick disease type C1 patients and zebrafish","volume":"22","author":"Louwette","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2021042501151019400_b53-0061089","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.neuron.2008.01.002","article-title":"Genetic dissection of neural circuits","volume":"57","author":"Luo","year":"2008","journal-title":"Neuron"},{"key":"2021042501151019400_b54-0061089","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1093\/hmg\/ddr505","article-title":"A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations","volume":"21","author":"Maue","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2021042501151019400_b55-0061089","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006239","article-title":"Epidemiology of Alzheimer disease","volume":"2012","author":"Mayeux","year":"2012","journal-title":"Cold Spring Harb. Perspect Med."},{"key":"2021042501151019400_b56-0061089","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2011.06.001","article-title":"Gaucher disease glucocerebrosidase and \u03b1-synuclein form a bidirectional pathogenic loop in synucleinopathies","volume":"146","author":"Mazzulli","year":"2011","journal-title":"Cell"},{"key":"2021042501151019400_b57-0061089","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1242\/dev.048967","article-title":"Evolutionary crossroads in developmental biology: sea urchins","volume":"138","author":"McClay","year":"2011","journal-title":"Development"},{"key":"2021042501151019400_b58-0061089","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/jama.281.3.249","article-title":"Prevalence of lysosomal storage disorders","volume":"281","author":"Meikle","year":"1999","journal-title":"JAMA"},{"key":"2021042501151019400_b59-0061089","first-page":"140","article-title":"Lysosome lipid storage disorder in NCTR-BALB\/c mice. I. Description of the disease and genetics","volume":"108","author":"Morris","year":"1982","journal-title":"Am. J. Pathol."},{"key":"2021042501151019400_b60-0061089","doi-asserted-by":"crossref","first-page":"23842","DOI":"10.1074\/jbc.M111.227645","article-title":"An \u2018exacerbate-reverse\u2019 strategy in yeast identifies histone deacetylase inhibition as a correction for cholesterol and sphingolipid transport defects in human Niemann-Pick type C disease","volume":"286","author":"Munkacsi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2021042501151019400_b61-0061089","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nn1876","article-title":"Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons","volume":"10","author":"Nagai","year":"2007","journal-title":"Nat. Neurosci."},{"key":"2021042501151019400_b62-0061089","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1126\/science.290.5500.2298","article-title":"Identification of HE1 as the second gene of Niemann-Pick C disease","volume":"290","author":"Naureckiene","year":"2000","journal-title":"Science"},{"key":"2021042501151019400_b63-0061089","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"2021042501151019400_b64-0061089","first-page":"1","article-title":"Ein unbekanntes Krankheitsbild","volume":"79","author":"Niemann","year":"1914","journal-title":"Jahrbuch f\u00fcr Kinderheilkunde"},{"key":"2021042501151019400_b65-0061089","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ymgme.2012.01.020","article-title":"Iminosugar-based inhibitors of glucosylceramide synthase prolong survival but paradoxically increase brain glucosylceramide levels in Niemann-Pick C mice","volume":"105","author":"Nietupski","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"2021042501151019400_b66-0061089","doi-asserted-by":"crossref","first-page":"590","DOI":"10.4161\/auto.6259","article-title":"Neurodegenerative lysosomal disorders: a continuum from development to late age","volume":"4","author":"Nixon","year":"2008","journal-title":"Autophagy"},{"key":"2021042501151019400_b67-0061089","doi-asserted-by":"crossref","first-page":"12473","DOI":"10.1073\/pnas.0405255101","article-title":"Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain","volume":"101","author":"Ohgami","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042501151019400_b68-0061089","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1093\/hmg\/dds090","article-title":"Disruption and therapeutic rescue of autophagy in a human neuronal model of Niemann Pick type C1","volume":"21","author":"Ordonez","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2021042501151019400_b69-0061089","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.bbrc.2011.08.096","article-title":"Npc1 deficiency in the C57BL\/6J genetic background enhances Niemann-Pick disease type C spleen pathology","volume":"413","author":"Parra","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021042501151019400_b70-0061089","article-title":"Niemann-Pick disease type C","volume-title":"GeneReviews","author":"Patterson","year":"1993"},{"key":"2021042501151019400_b71-0061089","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/jnr.20592","article-title":"Adenovirus expressing an NPC1-GFP fusion gene corrects neuronal and nonneuronal defects associated with Niemann pick type C disease","volume":"81","author":"Paul","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"2021042501151019400_b72-0061089","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bbalip.2004.08.005","article-title":"Niemann-Pick C research from mouse to gene","volume":"1685","author":"Pentchev","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"2021042501151019400_b73-0061089","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.1016\/S0021-9258(17)35852-0","article-title":"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","volume":"261","author":"Pentchev","year":"1986","journal-title":"J. Biol. Chem."},{"key":"2021042501151019400_b74-0061089","doi-asserted-by":"crossref","first-page":"6569","DOI":"10.1523\/JNEUROSCI.5529-07.2008","article-title":"Neuronal loss of Drosophila NPC1a causes cholesterol aggregation and age-progressive neurodegeneration","volume":"28","author":"Phillips","year":"2008","journal-title":"J. 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