RGD Reference Report - Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia. - Rat Genome Database

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Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia.

Authors: Davies, JP  Scott, C  Oishi, K  Liapis, A  Ioannou, YA 
Citation: Davies JP, etal., J Biol Chem. 2005 Apr 1;280(13):12710-20. Epub 2005 Jan 25.
RGD ID: 1642184
Pubmed: PMID:15671032   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M409110200   (Journal Full-text)

NPC1L1, a recently identified relative of Niemann-Pick C1, was characterized to determine its subcellular location and potential function(s). NPC1L1 was highly expressed in HepG2 cells and localized in a subcellular vesicular compartment rich in the small GTPase Rab5. mRNA expression profiling revealed significant differences between mouse and man with highest expression found in human liver and significant expression in the small intestine. In contrast, liver expression in mouse was extremely low with mouse small intestine exhibiting the highest NPC1L1 expression. A mouse knock-out model of NPC1L1 was generated and revealed that mice lacking a functional NPC1L1 have multiple lipid transport defects. Surprisingly, lack of NPC1L1 exerts a protective effect against diet-induced hyperlipidemia. Further characterization of cell lines generated from wild-type and knock-out mice revealed that in contrast to wild-type cells, NPC1L1 cells exhibit aberrant plasma membrane uptake and subsequent transport of various lipids, including cholesterol and sphingolipids. Furthermore, lack of NPC1L1 activity causes a deregulation of caveolin transport and localization, suggesting that the observed lipid transport defects may be the indirect result of an inability of NPC1L1 null cells to properly target and/or regulate caveolin expression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypercholesterolemia  ISONpc1l1 (Mus musculus)1642184; 1642184 RGD 
Hypercholesterolemia  IAGP 1642184 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Npc1l1  (NPC1 like intracellular cholesterol transporter 1)

Genes (Mus musculus)
Npc1l1  (NPC1 like intracellular cholesterol transporter 1)

Genes (Homo sapiens)
NPC1L1  (NPC1 like intracellular cholesterol transporter 1)


Additional Information