| http://purl.uniprot.org/citations/26019327 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26019327 | http://www.w3.org/2000/01/rdf-schema#comment | "Niemann-Pick Type C1 (NPC1) disease is a rare neurovisceral, cholesterol-sphingolipid lysosomal storage disorder characterized by ataxia, motor impairment, progressive intellectual decline, and dementia. The most prevalent mutation, NPC1(I1061T), encodes a misfolded protein with a reduced half-life caused by ER-associated degradation. Therapies directed at stabilization of the mutant NPC1 protein reduce cholesterol storage in fibroblasts but have not been tested in vivo because of lack of a suitable animal model. Whereas the prominent features of human NPC1 disease are replicated in the null Npc1(-/-) mouse, this model is not amenable to examining proteostatic therapies. The objective of the present study was to develop an NPC1 I1061T knock-in mouse in which to test proteostatic therapies. Compared with the Npc1(-/-) mouse, this Npc1(tm(I1061T)Dso) model displays a less severe, delayed form of NPC1 disease with respect to weight loss, decreased motor coordination, Purkinje cell death, lipid storage, and premature death. The murine NPC1(I1061T) protein has a reduced half-life in vivo, consistent with protein misfolding and rapid ER-associated degradation, and can be stabilized by histone deacetylase inhibition. This novel mouse model faithfully recapitulates human NPC1 disease and provides a powerful tool for preclinical evaluation of therapies targeting NPC1 protein variants with compromised stability."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.4173-14.2015"xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Chen Z."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Chung C."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Fujiwara H."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Schaffer J.E."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Sidhu R."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Davidson C."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Sikora J."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Lieberman A.P."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Walkley S.U."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Ory D.S."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Praggastis M."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Maxfield F.R."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Pipalia N.H."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Chacko A."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/author | "Tortelli B."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/pages | "8091-8106"xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/title | "A murine Niemann-Pick C1 I1061T knock-in model recapitulates the pathological features of the most prevalent human disease allele."xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://purl.uniprot.org/core/volume | "35"xsd:string |
| http://purl.uniprot.org/citations/26019327 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26019327 |