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

Journal Article

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.

Full Text

Duke Authors

Cited 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

Published Date

  • December 2000

Published In

Volume / Issue

  • 26 / 4

Start / End Page

  • 435 - 439

PubMed ID

  • 11101840

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/82565

Language

  • eng

Conference Location

  • United States