{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:22:35Z","timestamp":1782966155469,"version":"3.54.5"},"reference-count":56,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":345,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["1ZIAHG000068-15"],"award-info":[{"award-number":["1ZIAHG000068-15"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008028","name":"School of Medicine and Public Health, University of Wisconsin-Madison","doi-asserted-by":"publisher","award":["3T32GM008692"],"award-info":[{"award-number":["3T32GM008692"]}],"id":[{"id":"10.13039\/100008028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson's UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Niemann-Pick disease type C1 (NPC1) is a rare, fatal neurodegenerative disorder characterized by lysosomal accumulation of unesterified cholesterol and glycosphingolipids. These subcellular pathologies lead to phenotypes of hepatosplenomegaly, neurological degeneration and premature death. NPC1 is extremely heterogeneous in the timing of clinical presentation and is associated with a wide spectrum of causative NPC1 mutations. To study the genetic architecture of NPC1, we have generated a new NPC1 mouse model, Npc1em1Pav. Npc1em1Pav\/em1Pav mutants showed notably reduced NPC1 protein compared to controls and displayed the pathological and biochemical hallmarks of NPC1. Interestingly, Npc1em1Pav\/em1Pav mutants on a C57BL\/6J genetic background showed more severe visceral pathology and a significantly shorter lifespan compared to Npc1em1Pav\/em1Pav mutants on a BALB\/cJ background, suggesting that strain-specific modifiers contribute to disease severity and survival. QTL analysis for lifespan of 202 backcross N2 mutants on a mixed C57BL\/6J and BALB\/cJ background detected significant linkage to markers on chromosomes 1 and 7. The discovery of these modifier regions demonstrates that mouse models are powerful tools for analyzing the genetics underlying rare human diseases, which can be used to improve understanding of the variability in NPC1 phenotypes and advance options for patient diagnosis and therapy.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.042614","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T14:35:14Z","timestamp":1580308514000},"source":"Crossref","is-referenced-by-count":32,"title":["Genetic background modifies phenotypic severity and longevity in a mouse model of Niemann-Pick disease type C1"],"prefix":"10.1242","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-1281","authenticated-orcid":false,"given":"Jorge L.","family":"Rodriguez-Gil","sequence":"first","affiliation":[{"name":"Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 1 Genomics, Development and Disease Section ,"},{"name":"University of Oxford, Oxford OX1 3QT, UK 2 Department of Pharmacology ,"},{"name":"University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USA 3 Medical Scientist Training Program ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn E.","family":"Watkins-Chow","sequence":"additional","affiliation":[{"name":"Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 1 Genomics, Development and Disease Section ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Baxter","sequence":"additional","affiliation":[{"name":"Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 1 Genomics, Development and Disease Section ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene","family":"Elliot","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 4 Embryonic Stem Cell and Transgenic Mouse Core ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula L.","family":"Harper","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 5 Genomics Core ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Wincovitch","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 6 Cytogenetics and Microscopy Core ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Wedel","sequence":"additional","affiliation":[{"name":"Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 1 Genomics, Development and Disease Section ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo A.","family":"Incao","sequence":"additional","affiliation":[{"name":"Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 1 Genomics, Development and Disease Section ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mylene","family":"Huebecker","sequence":"additional","affiliation":[{"name":"University of Oxford, Oxford OX1 3QT, UK 2 Department of Pharmacology ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1644-5931","authenticated-orcid":false,"given":"Frederick J.","family":"Boehm","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison, Madison, WI 53706, USA 7 Department of Statistics ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Garver","sequence":"additional","affiliation":[{"name":"University of New Mexico, Albuquerque, NM 87131, USA 8 Department of Chemistry and Chemical Biology ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA 9 Program in Developmental Endocrinology and Genetics ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4914-6671","authenticated-orcid":false,"given":"Karl W.","family":"Broman","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison, Madison, WI 53726, USA 10 Department of Biostatistics and Medical Informatics ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-0403","authenticated-orcid":false,"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"University of Oxford, Oxford OX1 3QT, UK 2 Department of Pharmacology ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-5120","authenticated-orcid":false,"given":"William J.","family":"Pavan","sequence":"additional","affiliation":[{"name":"Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA 1 Genomics, Development and Disease Section ,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,3,13]]},"reference":[{"key":"2024061302391767600_DMM042614C1","doi-asserted-by":"publisher","first-page":"326ra23","DOI":"10.1126\/scitranslmed.aad9407","article-title":"Chronic administration of an HDAC inhibitor treats both neurological and systemic Niemann-Pick type C disease in a mouse model","volume":"8","author":"Alam","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"2024061302391767600_DMM042614C2","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/nrg3031","article-title":"Exome sequencing as a tool for Mendelian disease gene discovery","volume":"12","author":"Bamshad","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"2024061302391767600_DMM042614C3","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1007\/s00415-014-7619-x","article-title":"Phenotypic heterogeneity of Niemann-Pick disease type C in monozygotic twins","volume":"262","author":"Benussi","year":"2015","journal-title":"J. Neurol."},{"key":"2024061302391767600_DMM042614C4","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1534\/genetics.118.301595","article-title":"R\/qtl2: software for mapping quantitative trait loci with high-dimensional data and multiparent populations","volume":"211","author":"Broman","year":"2019","journal-title":"Genetics"},{"key":"2024061302391767600_DMM042614C5","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ymgmr.2018.05.001","article-title":"Controversies on the potential therapeutic use of rapamycin for treating a lysosomal cholesterol storage disease","volume":"15","author":"Calder\u00f3n","year":"2018","journal-title":"Mol. Genet. Metab. Rep."},{"key":"2024061302391767600_DMM042614C6","doi-asserted-by":"publisher","first-page":"e46688","DOI":"10.1371\/journal.pone.0046688","article-title":"Predicting the functional effect of amino acid substitutions and indels","volume":"7","author":"Choi","year":"2012","journal-title":"PLoS ONE"},{"key":"2024061302391767600_DMM042614C7","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1534\/genetics.109.105486","article-title":"A new standard genetic map for the laboratory mouse","volume":"182","author":"Cox","year":"2009","journal-title":"Genetics"},{"key":"2024061302391767600_DMM042614C8","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1086\/302938","article-title":"Phenotypes of patients with \u201csimple\u201d Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics","volume":"66","author":"Dipple","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"2024061302391767600_DMM042614C9","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/nrg.2017.52","article-title":"Settling the score: variant prioritization and Mendelian disease","volume":"18","author":"Eilbeck","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"2024061302391767600_DMM042614C10","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/hmg\/ddp552","article-title":"Conditional Niemann-Pick C mice demonstrate cell autonomous Purkinje cell neurodegeneration","volume":"19","author":"Elrick","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"2024061302391767600_DMM042614C11","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13023-015-0240-y","article-title":"Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C","volume":"10","author":"Fecarotta","year":"2015","journal-title":"Orphanet. J. Rare. Dis."},{"key":"2024061302391767600_DMM042614C12","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1080\/17460441.2019.1588882","article-title":"Animal models for Niemann-Pick type C: implications for drug discovery & development","volume":"14","author":"Fog","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"2024061302391767600_DMM042614C13","doi-asserted-by":"publisher","first-page":"8229","DOI":"10.1074\/jbc.M708735200","article-title":"Niemann-Pick type C1 I1061T mutant encodes a functional protein that is selected for endoplasmic reticulum-associated degradation due to protein misfolding","volume":"283","author":"Gelsthorpe","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2024061302391767600_DMM042614C14","doi-asserted-by":"publisher","first-page":"41931","DOI":"10.1038\/srep41931","article-title":"New murine Niemann-Pick type C models bearing a pseudoexon-generating mutation recapitulate the main neurobehavioural and molecular features of the disease","volume":"7","author":"G\u00f3mez-Grau","year":"2017","journal-title":"Sci. Rep."},{"key":"2024061302391767600_DMM042614C15","doi-asserted-by":"publisher","first-page":"e1787","DOI":"10.3791\/1787","article-title":"A simple composite phenotype scoring system for evaluating mouse models of cerebellar ataxia","volume":"39","author":"Guyenet","year":"2010","journal-title":"J. Vis. Exp."},{"key":"2024061302391767600_DMM042614C16","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1186\/s12883-015-0511-1","article-title":"Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: a 5-year update from the UK clinical database","volume":"15","author":"Imrie","year":"2015","journal-title":"BMC Neurol."},{"key":"2024061302391767600_DMM042614C17","doi-asserted-by":"publisher","first-page":"e53565","DOI":"10.3791\/53565","article-title":"Generating primary fibroblast cultures from mouse ear and tail tissues","volume":"107","author":"Khan","year":"2016","journal-title":"J. Vis. Exp."},{"key":"2024061302391767600_DMM042614C18","doi-asserted-by":"publisher","first-page":"355ra118","DOI":"10.1126\/scitranslmed.aad9823","article-title":"Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses","volume":"8","author":"Kirkegaard","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"2024061302391767600_DMM042614C19","doi-asserted-by":"publisher","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":"2024061302391767600_DMM042614C20","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1534\/genetics.114.161653","article-title":"High-resolution sex-specific linkage maps of the mouse reveal polarized distribution of crossovers in male germline","volume":"197","author":"Liu","year":"2014","journal-title":"Genetics"},{"key":"2024061302391767600_DMM042614C21","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1042\/BST0381458","article-title":"Endolysosomal calcium regulation and disease","volume":"38","author":"Lloyd-Evans","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"2024061302391767600_DMM042614C22","doi-asserted-by":"publisher","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":"2024061302391767600_DMM042614C23","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1534\/genetics.106.061549","article-title":"Poor performance of bootstrap confidence intervals for the location of a quantitative trait locus","volume":"174","author":"Manichaikul","year":"2006","journal-title":"Genetics"},{"key":"2024061302391767600_DMM042614C24","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.gene.2017.12.006","article-title":"In Niemann-Pick C1 mouse models, glial-only expression of the normal gene extends survival much further than do changes in genetic background or treatment with hydroxypropyl-beta-cyclodextrin","volume":"643","author":"Marshall","year":"2018","journal-title":"Gene"},{"key":"2024061302391767600_DMM042614C25","doi-asserted-by":"publisher","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":"2024061302391767600_DMM042614C26","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1086\/302626","article-title":"Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype","volume":"65","author":"Millat","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"2024061302391767600_DMM042614C27","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1086\/320606","article-title":"Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop","volume":"68","author":"Millat","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"2024061302391767600_DMM042614C28","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.ymgme.2005.07.007","article-title":"Niemann-Pick C disease: use of denaturing high performance liquid chromatography for the detection of NPC1 and NPC2 genetic variations and impact on management of patients and families","volume":"86","author":"Millat","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"2024061302391767600_DMM042614C29","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1002\/pst.1848","article-title":"Approaches to sample size calculation for clinical trials in rare diseases","volume":"17","author":"Miller","year":"2018","journal-title":"Pharm. Stat."},{"key":"2024061302391767600_DMM042614C30","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1093\/oxfordjournals.jhered.a110265","article-title":"A mouse model for Niemann-Pick disease: influence of genetic background on disease expression in spm\/spm mice","volume":"77","author":"Miyawaki","year":"1986","journal-title":"J. Hered."},{"key":"2024061302391767600_DMM042614C31","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1534\/g3.115.022087","article-title":"The mouse universal genotyping array: from substrains to subspecies","volume":"6","author":"Morgan","year":"2015","journal-title":"G3 (Bethesda)"},{"key":"2024061302391767600_DMM042614C56","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/35056009","article-title":"Modifier genes in mice and humans","volume":"2","author":"Nadeau","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"2024061302391767600_DMM042614C32","doi-asserted-by":"publisher","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":"2024061302391767600_DMM042614C33","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.ab.2004.03.051","article-title":"Analysis of fluorescently labeled glycosphingolipid-derived oligosaccharides following ceramide glycanase digestion and anthranilic acid labeling","volume":"331","author":"Neville","year":"2004","journal-title":"Anal. Biochem."},{"key":"2024061302391767600_DMM042614C34","doi-asserted-by":"publisher","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":"2024061302391767600_DMM042614C35","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13023-015-0284-z","article-title":"Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study","volume":"10","author":"Patterson","year":"2015","journal-title":"Orphanet. J. Rare. Dis."},{"key":"2024061302391767600_DMM042614C36","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3390\/ijms19010325","article-title":"Heat shock proteins and autophagy pathways in neuroprotection: from molecular bases to pharmacological interventions","volume":"19","author":"Penke","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2024061302391767600_DMM042614C37","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0025-4","article-title":"Lysosomal storage diseases","volume":"4","author":"Platt","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2024061302391767600_DMM042614C38","doi-asserted-by":"publisher","first-page":"8091","DOI":"10.1523\/JNEUROSCI.4173-14.2015","article-title":"A murine Niemann-Pick C1 I1061T knock-in model recapitulates the pathological features of the most prevalent human disease allele","volume":"35","author":"Praggastis","year":"2015","journal-title":"J. Neurosci."},{"key":"2024061302391767600_DMM042614C39","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nrneurol.2017.148","article-title":"Antisense oligonucleotides: the next frontier for treatment of neurological disorders","volume":"14","author":"Rinaldi","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"2024061302391767600_DMM042614C55","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.ajhg.2017.06.004","article-title":"From peas to disease: modifier genes, network resilience, and the genetics of health","volume":"101","author":"Riordan","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"2024061302391767600_DMM042614C40","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ymgme.2013.06.010","article-title":"A somatic cell defect is associated with the onset of neurological symptoms in a lysosomal storage disease","volume":"110","author":"Rodriguez-Gil","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"2024061302391767600_DMM042614C41","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S0168-9525(99)01761-8","article-title":"Monogenic traits are not simple: lessons from phenylketonuria","volume":"15","author":"Scriver","year":"1999","journal-title":"Trends Genet."},{"key":"2024061302391767600_DMM042614C42","doi-asserted-by":"publisher","first-page":"5292","DOI":"10.1038\/s41598-019-41707-y","article-title":"Different Niemann-Pick C1 genotypes generate protein phenotypes that vary in their intracellular processing, trafficking and localization","volume":"9","author":"Shammas","year":"2019","journal-title":"Sci. Rep."},{"key":"2024061302391767600_DMM042614C43","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1097\/NEN.0b013e31825414a6","article-title":"Miglustat improves purkinje cell survival and alters microglial phenotype in feline Niemann-Pick disease type C","volume":"71","author":"Stein","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2024061302391767600_DMM042614C44","doi-asserted-by":"publisher","first-page":"26167","DOI":"10.1074\/jbc.M311591200","article-title":"Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport","volume":"279","author":"te Vruchte","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2024061302391767600_DMM042614C45","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1172\/JCI72835","article-title":"Relative acidic compartment volume as a lysosomal storage disorder-associated biomarker","volume":"124","author":"te Vruchte","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2024061302391767600_DMM042614C46","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1750-1172-5-16","article-title":"Niemann-Pick disease type C","volume":"5","author":"Vanier","year":"2010","journal-title":"Orphanet. J. Rare. Dis."},{"key":"2024061302391767600_DMM042614C47","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1034\/j.1399-0004.2003.00147.x","article-title":"Niemann-Pick disease type C","volume":"64","author":"Vanier","year":"2003","journal-title":"Clin. Genet."},{"key":"2024061302391767600_DMM042614C48","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1111\/j.1399-0004.1988.tb03460.x","article-title":"Niemann-Pick disease group C: clinical variability and diagnosis based on defective cholesterol esterification: a collaborative study on 70 patients","volume":"33","author":"Vanier","year":"1988","journal-title":"Clin. Genet."},{"key":"2024061302391767600_DMM042614C49","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/0925-4439(91)90069-L","article-title":"Type C Niemann-Pick disease: spectrum of phenotypic variation in disruption of intracellular LDL-derived cholesterol processing","volume":"1096","author":"Vanier","year":"1991","journal-title":"Biochim. Biophys. Acta"},{"key":"2024061302391767600_DMM042614C50","doi-asserted-by":"publisher","first-page":"S221","DOI":"10.1007\/s10545-009-1173-1","article-title":"Gender dimorphism in siblings with schizophrenia-like psychosis due to Niemann-Pick disease type C","volume":"32","author":"Walterfang","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"2024061302391767600_DMM042614C51","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1534\/g3.116.038091","article-title":"Highly efficient Cpf1-mediated gene targeting in mice following high concentration pronuclear injection","volume":"7","author":"Watkins-Chow","year":"2017","journal-title":"G3 (Bethesda)"},{"key":"2024061302391767600_DMM042614C52","doi-asserted-by":"publisher","first-page":"15330","DOI":"10.1073\/pnas.1112751108","article-title":"Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice","volume":"108","author":"Xie","year":"2011","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2024061302391767600_DMM042614C53","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/S0960-9822(01)00396-7","article-title":"Critical role for glycosphingolipids in Niemann-Pick disease type C","volume":"11","author":"Zervas","year":"2001","journal-title":"Curr. Biol."},{"key":"2024061302391767600_DMM042614C54","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s003350010013","article-title":"A modifier of Niemann Pick C 1 maps to mouse chromosome 19","volume":"11","author":"Zhang","year":"2000","journal-title":"Mamm. Genome"}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dmm.042614","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.042614\/3484802\/dmm042614.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.042614\/2065740\/dmm_042614v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.042614\/3484802\/dmm042614.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T02:39:38Z","timestamp":1718246378000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/13\/3\/dmm042614\/225203\/Genetic-background-modifies-phenotypic-severity"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,1]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.042614","relation":{},"ISSN":["1754-8411","1754-8403"],"issn-type":[{"value":"1754-8411","type":"electronic"},{"value":"1754-8403","type":"print"}],"subject":[],"published":{"date-parts":[[2020,3,1]]},"article-number":"dmm042614"}}