{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:13:18Z","timestamp":1780405998595,"version":"3.54.1"},"reference-count":66,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["3T32GM008692"],"award-info":[{"award-number":["3T32GM008692"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The rare lysosomal storage disorder Niemann-Pick disease type C1 (NPC1) arises from mutation of NPC1, which encodes a lysosomal transmembrane protein essential for normal transport and trafficking of cholesterol and sphingolipids. NPC1 is highly heterogeneous in both clinical phenotypes and age of onset. Previous studies have reported sub-Mendelian survival rates for mice homozygous for various Npc1 mutant alleles but have not studied the potential mechanisms underlying this phenotype. We performed the first developmental analysis of a Npc1 mouse model, Npc1em1Pav, and discovered significant fetal growth restriction in homozygous mutants beginning at E16.5. Npc1em1Pav\/em1Pav mice also exhibited cyanosis, increased respiratory effort, and over 50% lethality at birth. Analysis of neonatal lung tissues revealed lipid accumulation, notable abnormalities in surfactant, and enlarged alveolar macrophages, suggesting that lung abnormalities may be associated with neonatal lethality in Npc1em1Pav\/em1Pav mice. The phenotypic severity of the Npc1em1Pav model facilitated this first analysis of perinatal lethality and lung pathology in an NPC1 model organism, and this model may serve as a useful resource for developing treatments for respiratory complications seen in NPC1 patients.<\/jats:p>","DOI":"10.3390\/jcm9010012","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T03:23:12Z","timestamp":1577071392000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["NPC1 Deficiency in Mice is Associated with Fetal Growth Restriction, Neonatal Lethality and Abnormal Lung Pathology"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-1281","authenticated-orcid":false,"given":"Jorge L.","family":"Rodriguez-Gil","sequence":"first","affiliation":[{"name":"Genomics, Development and Disease Section, Genetic Disease Research Branch, NHGRI, NIH, Bethesda, MD 20892, USA"},{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"},{"name":"Medical Scientist Training Program, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53726, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn E.","family":"Watkins-Chow","sequence":"additional","affiliation":[{"name":"Genomics, Development and Disease Section, Genetic Disease Research Branch, NHGRI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Baxter","sequence":"additional","affiliation":[{"name":"Genomics, Development and Disease Section, Genetic Disease Research Branch, NHGRI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadafumi","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Section of Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NHGRI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"Zerfas","sequence":"additional","affiliation":[{"name":"Office of Research Services, Division of Veterinary Resources, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew F.","family":"Starost","sequence":"additional","affiliation":[{"name":"Office of Research Services, Division of Veterinary Resources, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"Section of Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NHGRI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May Christine V.","family":"Malicdan","sequence":"additional","affiliation":[{"name":"Section of Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NHGRI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Program in Developmental Endocrinology and Genetics, NICHD, NIH, Bethesda, MD 20892, USA"}],"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":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Pavan","sequence":"additional","affiliation":[{"name":"Genomics, Development and Disease Section, Genetic Disease Research Branch, NHGRI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","first-page":"27","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":"ref_3","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":"ref_4","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":"ref_5","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0925-4439(94)90021-3","article-title":"Free sphingoid bases in tissues from patients with type C Niemann-Pick disease and other lysosomal storage disorders","volume":"1226","author":"Rousson","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1016\/j.febslet.2010.04.047","article-title":"Defective cholesterol trafficking in Niemann-Pick C-deficient cells","volume":"584","author":"Peake","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10079","DOI":"10.1073\/pnas.1611956113","article-title":"Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2","volume":"113","author":"Li","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1086\/302620","article-title":"Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain","volume":"65","author":"Greer","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","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":"ref_10","doi-asserted-by":"crossref","first-page":"9116","DOI":"10.1073\/pnas.1711716114","article-title":"3.3 \u00c5 structure of Niemann-Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport","volume":"114","author":"Li","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41586-018-0308-7","article-title":"Structures of human Patched and its complex with native palmitoylated sonic hedgehog","volume":"560","author":"Qi","year":"2018","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.cell.2018.10.026","article-title":"Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched","volume":"175","author":"Zhang","year":"2018","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1750-1172-8-12","article-title":"Disease and patient characteristics in NP-C patients: Findings from an international disease registry","volume":"8","author":"Patterson","year":"2013","journal-title":"Orphanet. J. Rare. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13023-018-0785-7","article-title":"Consensus clinical management guidelines for Niemann-Pick disease type C","volume":"13","author":"Geberhiwot","year":"2018","journal-title":"Orphanet. J. Rare. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1002\/ajmg.a.31735","article-title":"The National Niemann-Pick C1 disease database: Report of clinical features and health problems","volume":"143A","author":"Garver","year":"2007","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_16","doi-asserted-by":"crossref","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":"ref_17","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1136\/adc.64.10_Spec_No.1391","article-title":"Fetal ascites: An unusual presentation of Niemann-Pick disease type C","volume":"64","author":"Maconochie","year":"1989","journal-title":"Arch. Dis. Child."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1136\/adc.65.3.335-e","article-title":"Fetal ascites: An unusual presentation of Niemann-Pick disease type C","volume":"65","author":"Manning","year":"1990","journal-title":"Arch. Dis. Child."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1111\/j.1651-2227.2008.00829.x","article-title":"Prenatal revelation of Niemann-Pick disease type C in siblings","volume":"97","author":"Moreno","year":"2008","journal-title":"Acta Paediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/ajmg.a.32642","article-title":"The clinical spectrum of fetal Niemann-Pick type C","volume":"149A","author":"Spiegel","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.pedneo.2013.01.015","article-title":"Prenatal-onset Niemann-Pick type C disease with nonimmune hydrops fetalis","volume":"54","author":"Yakarisik","year":"2013","journal-title":"Pediatr. Neonatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/8904_2015_516","article-title":"In Utero Diagnosis of Niemann-Pick Type C in the Absence of Family History","volume":"28","author":"Colin","year":"2016","journal-title":"JIMD Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1007\/s00431-017-3020-y","article-title":"Niemann-Pick disease type C in the newborn period: A single-center experience","volume":"176","author":"Gumus","year":"2017","journal-title":"Eur. J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1007\/s00431-018-3219-6","article-title":"Pulmonary involvement in Niemann-Pick C type 1","volume":"177","author":"Aviram","year":"2018","journal-title":"Eur. J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"FSO63","DOI":"10.4155\/fso.15.63","article-title":"Animal models are essential to biological research: Issues and perspectives","volume":"1","author":"Montagutelli","year":"2015","journal-title":"Future Sci. OA"},{"key":"ref_26","doi-asserted-by":"crossref","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":"ref_27","doi-asserted-by":"crossref","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":"ref_28","doi-asserted-by":"crossref","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":"ref_29","doi-asserted-by":"crossref","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":"ref_30","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":"ref_31","doi-asserted-by":"crossref","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":"Casas","year":"2017","journal-title":"Sci Rep."},{"key":"ref_32","doi-asserted-by":"crossref","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":"ref_33","doi-asserted-by":"crossref","unstructured":"Albert, M., Schmitz, S.U., Kooistra, S.M., Malatesta, M., Morales Torres, C., Rekling, J.C., Johansen, J.V., Abarrategui, I., and Helin, K. (2013). The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003461"},{"key":"ref_34","doi-asserted-by":"crossref","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":"ref_35","doi-asserted-by":"crossref","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":"ref_36","doi-asserted-by":"crossref","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":"ref_37","doi-asserted-by":"crossref","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":"ref_38","doi-asserted-by":"crossref","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"},{"key":"ref_39","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":"ref_40","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.aanat.2016.08.003","article-title":"Lung surfactant: Function and composition in the context of development and respiratory physiology","volume":"208","author":"Bernhard","year":"2016","journal-title":"Ann. Anat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R207","DOI":"10.1093\/hmg\/ddh252","article-title":"Genetic disorders influencing lung formation and function at birth","volume":"13","author":"Whitsett","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000101347","article-title":"Genetic disorders of surfactant proteins","volume":"91","author":"Hamvas","year":"2007","journal-title":"Neonatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1002\/ppul.20725","article-title":"Lung disease in Niemann-Pick disease","volume":"42","author":"Guillemot","year":"2007","journal-title":"Pediatr. Pulmonol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0925-4439(98)00061-1","article-title":"The role of lipids in pulmonary surfactant","volume":"1408","author":"Veldhuizen","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1056\/NEJMra022387","article-title":"Hydrophobic surfactant proteins in lung function and disease","volume":"347","author":"Whitsett","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bbalip.2005.09.002","article-title":"Pulmonary surfactant function is abolished by an elevated proportion of cholesterol","volume":"1737","author":"Gunasekara","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"L117","DOI":"10.1152\/ajplung.00218.2009","article-title":"Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury","volume":"298","author":"Vockeroth","year":"2010","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"L919","DOI":"10.1152\/ajplung.00383.2011","article-title":"Characterization of the Niemann-Pick C pathway in alveolar type II cells and lamellar bodies of the lung","volume":"302","author":"Roszell","year":"2012","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Roszell, B.R., Tao, J.-Q., Yu, K.J., Gao, L., Huang, S., Ning, Y., Feinstein, S.I., Vite, C.H., and Bates, S.R. (2013). Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067084"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1083\/jcb.4.6.693","article-title":"The ultrastructure of mouse lung: The alveolar macrophage","volume":"4","author":"Karrer","year":"1958","journal-title":"J. Biophys. Biochem. Cytol."},{"key":"ref_51","first-page":"L1","article-title":"Surfactant protein A and surfactant protein D in health and disease","volume":"275","author":"Mason","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000047051","article-title":"Lung surfactant proteins A and D in innate immune defense","volume":"77","author":"Vaandrager","year":"2000","journal-title":"Biol. Neonate"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0022-3476(05)81695-6","article-title":"Niemann-Pick disease type C: Diagnosis and outcome in children, with particular reference to liver disease","volume":"123","author":"Kelly","year":"1993","journal-title":"J. Pediatr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1177\/088307389801300206","article-title":"Nova Scotia Niemann-Pick disease (type D): Clinical study of 20 cases","volume":"13","author":"Jan","year":"1998","journal-title":"J. Child Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1750-1172-7-76","article-title":"Dysphagia as a risk factor for mortality in Niemann-Pick disease type C: Systematic literature review and evidence from studies with miglustat","volume":"7","author":"Walterfang","year":"2012","journal-title":"Orphanet. J. Rare. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4137\/CMPed.S40070","article-title":"Intrauterine Growth Restriction: Antenatal and Postnatal Aspects","volume":"10","author":"Sharma","year":"2016","journal-title":"Clin. Med. Insights Pediatr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1126\/science.274.5285.255","article-title":"Cholesterol modification of hedgehog signaling proteins in animal development","volume":"274","author":"Porter","year":"1996","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1007\/PL00000653","article-title":"The role of cholesterol in Shh signaling and teratogen-induced holoprosencephaly","volume":"57","author":"Incardona","year":"2000","journal-title":"Cell Mol. Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/S0002-9297(07)62934-6","article-title":"The sonic hedgehog-patched-gli pathway in human development and disease","volume":"67","author":"Villavicencio","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Bidet, M., Joubert, O., Lacombe, B., Ciantar, M., Nehm\u00e9, R., Mollat, P., Br\u00e9tillon, L., Faure, H., Bittman, R., and Ruat, M. (2011). The hedgehog receptor patched is involved in cholesterol transport. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023834"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.molcel.2017.02.015","article-title":"Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling","volume":"66","author":"Xiao","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"R119","DOI":"10.1093\/hmg\/ddy155","article-title":"The pathogenesis of lysosomal storage disorders: Beyond the engorgement of lysosomes to abnormal development and neuroinflammation","volume":"27","author":"Fiorenza","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1093\/hmg\/ddx118","article-title":"Shortened primary cilium length and dysregulated Sonic hedgehog signaling in Niemann-Pick C1 disease","volume":"26","author":"Canterini","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/jcp.25926","article-title":"Primary cilium alterations and expression changes of Patched1 proteins in niemann-pick type C disease","volume":"233","author":"Formichi","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.nbd.2014.06.012","article-title":"A marked paucity of granule cells in the developing cerebellum of the Npc1(-\/-) mouse is corrected by a single injection of hydroxypropyl-\u03b2-cyclodextrin","volume":"70","author":"Nusca","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1093\/hmg\/ddv042","article-title":"Analysis of hedgehog signaling in cerebellar granule cell precursors in a conditional Nsdhl allele demonstrates an essential role for cholesterol in postnatal CNS development","volume":"24","author":"Cunningham","year":"2015","journal-title":"Hum. Mol. Genet."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/1\/12\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:43:41Z","timestamp":1760190221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/1\/12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,19]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["jcm9010012"],"URL":"https:\/\/doi.org\/10.3390\/jcm9010012","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,19]]}}}