title: Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production.
abstract: 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.
authors: Centre de Recherche de Hôpital Laval et Centre de Recherche sur le Métabolisme Energétique, Université Laval, Québec, Canada.
authors: D
authors: D
authors: Arsenijevic
authors: H
authors: H
authors: Onuma
authors: C
authors: C
authors: Pecqueur
authors: S
authors: S
authors: Raimbault
authors: B S
authors: BS
authors: Manning
authors: B
authors: B
authors: Miroux
authors: E
authors: E
authors: Couplan
authors: M C
authors: MC
authors: Alves-Guerra
authors: M
authors: M
authors: Goubern
authors: R
authors: R
authors: Surwit
authors: F
authors: F
authors: Bouillaud
authors: D
authors: D
authors: Richard
authors: S
authors: S
authors: Collins
authors: D
authors: D
authors: Ricquier
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting; D007109:Immunity / Q000235:genetics*; D007473:Ion Channels; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D011506:Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014475:Uncoupling Agents / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D017931:DNA Primers; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D017382:Reactive Oxygen Species; C000604390:Ucp2 protein, mouse; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2