title: The use of the Cre/loxP system to study oxidative stress in tissue-specific manganese superoxide dismutase knockout models.
abstract: CONCLUSIONS
  Respiring mitochondria are a significant site for reactions involving reactive oxygen and nitrogen species that contribute to irreversible cellular, structural, and functional damage leading to multiple pathological conditions. Manganese superoxide dismutase (MnSOD) is a critical component of the antioxidant system tasked with protecting the oxidant-sensitive mitochondrial compartment from oxidative stress. Since global knockout of MnSOD results in significant cardiac and neuronal damage leading to early postnatal lethality, this approach has limited use for studying the mechanisms of oxidant stress and the development of disease in specific tissues lacking MnSOD. To circumvent this problem, a number of investigators have employed the Cre/loxP system to precisely knockout MnSOD in individual tissues.
  
  
  BACKGROUND
  Multiple tissue and organ-specific Cre-expressing mice have been generated, which greatly enhance the specificity of MnSOD knockout in tissues and organ systems that were once difficult, if not impossible to study.
  
  
  RESULTS
  Evaluating the contribution of MnSOD deficiency to oxidant-mediated mitochondrial damage requires careful consideration of the promoter system used for creating the tissue-specific knockout animal, in addition to the collection and interpretation of multiple indices of oxidative stress and damage.
  
  
  CONCLUSIONS
  Expanded use of well-characterized tissue-specific promoter elements and inducible systems to drive the Cre/loxP recombinational events will lead to a spectrum of MnSOD tissue knockout models, and a clearer understanding of the role of MnSOD in preventing mitochondrial dysfunction in human disease.
authors: 1 Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences , Little Rock, Arkansas.
authors: John C
authors: JC
authors: Marecki
authors: Nirmala
authors: N
authors: Parajuli
authors: John P
authors: JP
authors: Crow
authors: Lee Ann
authors: LA
authors: MacMillan-Crow
mesh_terms: D000818:Animals; D015870:Gene Expression; D055786:Gene Knockout Techniques; D005818:Genetic Engineering; D006801:Humans; D019426:Integrases / Q000235:genetics; D009928:Organ Specificity; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D019426:Integrases; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C045073:Cre recombinase
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