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

Nat Genet. 2000 Dec;26(4):435-9. doi: 10.1038/82565.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Gene Expression
  • Gene Targeting
  • Immunity / genetics*
  • Ion Channels
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Membrane Transport Proteins*
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins*
  • Proteins / genetics*
  • Proteins / immunology
  • Proteins / metabolism
  • Reactive Oxygen Species / metabolism*
  • Toxoplasmosis, Animal / genetics
  • Toxoplasmosis, Animal / immunology
  • Toxoplasmosis, Animal / metabolism
  • Uncoupling Agents / metabolism
  • Uncoupling Protein 2


  • DNA Primers
  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Proteins
  • Reactive Oxygen Species
  • Ucp2 protein, mouse
  • Uncoupling Agents
  • Uncoupling Protein 2