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

Publication ,  Journal Article
Arsenijevic, D; Onuma, H; Pecqueur, C; Raimbault, S; Manning, BS; Miroux, B; Couplan, E; Alves-Guerra, MC; Goubern, M; Surwit, R; Bouillaud, F ...
Published in: Nat Genet
December 2000

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.

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Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

December 2000

Volume

26

Issue

4

Start / End Page

435 / 439

Location

United States

Related Subject Headings

  • Uncoupling Protein 2
  • Uncoupling Agents
  • Toxoplasmosis, Animal
  • Reactive Oxygen Species
  • Proteins
  • Mitochondrial Proteins
  • Mice, Knockout
  • Mice
  • Membrane Transport Proteins
  • Male
 

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Arsenijevic, D., Onuma, H., Pecqueur, C., Raimbault, S., Manning, B. S., Miroux, B., … Ricquier, D. (2000). Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet, 26(4), 435–439. https://doi.org/10.1038/82565
Arsenijevic, D., H. Onuma, C. Pecqueur, S. Raimbault, B. S. Manning, B. Miroux, E. Couplan, et al. “Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production.Nat Genet 26, no. 4 (December 2000): 435–39. https://doi.org/10.1038/82565.
Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Manning BS, Miroux B, et al. 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.
Arsenijevic, D., et al. “Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production.Nat Genet, vol. 26, no. 4, Dec. 2000, pp. 435–39. Pubmed, doi:10.1038/82565.
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. 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):435–439.

Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

December 2000

Volume

26

Issue

4

Start / End Page

435 / 439

Location

United States

Related Subject Headings

  • Uncoupling Protein 2
  • Uncoupling Agents
  • Toxoplasmosis, Animal
  • Reactive Oxygen Species
  • Proteins
  • Mitochondrial Proteins
  • Mice, Knockout
  • Mice
  • Membrane Transport Proteins
  • Male