RGD Reference Report - Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production.

Authors: Arsenijevic, D  Onuma, H  Pecqueur, C  Raimbault, S  Manning, BS  Miroux, B  Couplan, E  Alves-Guerra, MC  Goubern, M  Surwit, R  Bouillaud, F  Richard, D  Collins, S  Ricquier, D 
Citation: Arsenijevic D, etal., Nat Genet 2000 Dec;26(4):435-9.
RGD ID: 737759
Pubmed: PMID:11101840   (View Abstract at PubMed)
DOI: DOI:10.1038/82565   (Journal Full-text)

The gene Ucp2 is a member of a family of genes found in animals and plants, encoding a protein homologous to the brown fat uncoupling protein Ucp1 (refs 1-3). As Ucp2 is widely expressed in mammalian tissues, uncouples respiration and resides within a region of genetic linkage to obesity, a role in energy dissipation has been proposed. We demonstrate here, however, that mice lacking Ucp2 following targeted gene disruption are not obese and have a normal response to cold exposure or high-fat diet. Expression of Ucp2 is robust in spleen, lung and isolated macrophages, suggesting a role for Ucp2 in immunity or inflammatory responsiveness. We investigated the response to infection with Toxoplasma gondii in Ucp2-/- mice, and found that they are completely resistant to infection, in contrast with the lethality observed in wild-type littermates. Parasitic cysts and inflammation sites in brain were significantly reduced in Ucp2-/- mice (63% decrease, P<0.04). Macrophages from Ucp2-/- mice generated more reactive oxygen species than wild-type mice (80% increase, P<0.001) in response to T. gondii, and had a fivefold greater toxoplasmacidal activity in vitro compared with wild-type mice (P<0.001 ), which was absent in the presence of a quencher of reactive oxygen species (ROS). Our results indicate a role for Ucp2 in the limitation of ROS and macrophage-mediated immunity.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
UCP2Humantoxoplasmosis susceptibilityISOUcp2 (Mus musculus) RGD 
Ucp2Rattoxoplasmosis susceptibilityISOUcp2 (Mus musculus) RGD 
Ucp2Mousetoxoplasmosis susceptibilityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ucp2  (uncoupling protein 2)

Genes (Mus musculus)
Ucp2  (uncoupling protein 2 (mitochondrial, proton carrier))

Genes (Homo sapiens)
UCP2  (uncoupling protein 2)


Additional Information