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Gene Review

Gpx2  -  glutathione peroxidase 2

Mus musculus

Synonyms: GI-GPx, GPx-2, GPx-GI, GSHPx-2, GSHPx-GI, ...
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Disease relevance of Gpx2

  • We have previously demonstrated that targeted disruption of both the Gpx1 and Gpx2 genes (GPX-DKO) results in a high incidence of ileocolitis in mice raised under conventional conditions, which include the harboring of Helicobacter species [non-specific-pathogen-free (non-SPF) conditions] [1].
  • Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes [1].
  • Mice with combined disruption of Gpx1 and Gpx2 genes have colitis [2].
  • Although homozygous mice deficient in either the Gpx1 or Gpx2 gene appeared to be normal under standard housing conditions, homozygous mice deficient in both genes, double-knockout (KO) mice, had symptoms and pathology consistent with inflammatory bowel disease [2].

High impact information on Gpx2

  • We reported previously that approximately 25% of B6.129 Gpx1/2-DKO mice develop ileocolonic tumors by 6 to 9 months of age, when their non-DKO littermates [having at least one wild-type (WT) Gpx1 or Gpx2 allele] rarely have inflammation and none have tumors [3].
  • Glutathione Peroxidase 2, the Major Cigarette Smoke-Inducible Isoform of GPX in Lungs, Is Regulated by Nrf2 [4].
  • The results show that a trace amount of Gpx2 is protective against ileocolitis, and Se-deficient young Gpx1(+/-)Gpx2(-/-) mice will develop pathology and symptoms similar to Se-adequate Gpx1(-/-)Gpx2(-/-) mice [5].
  • Both Gpx1 and Gpx2 activities and mRNA levels were significantly depressed in the ileum of Se-deprived mice [5].
  • Some of the most significant changes in gene expression reflect changes in glutathione synthesis and redox regulation of the cell, including upregulation of glutathione S-transferase alpha-2, glutathione peroxidase 2, and glutamate-cysteine ligase, catalytic subunit (also known as gamma-glutamyl cysteine synthetase) [6].

Biological context of Gpx2


Anatomical context of Gpx2

  • Because a small percentage of Se-sufficient Gpx1(+/-)Gpx2(-/-) mice have mild ileocolitis, we hypothesized that Se-deficient Gpx1(+/-)Gpx2(-/-) mice will develop severe ileocolitis similarly to the Gpx1(-/-)Gpx2(-/-) mice, and even a trace amount of Gpx2 can protect intestinal mucosa against inflammation [5].


  1. Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Chu, F.F., Esworthy, R.S., Chu, P.G., Longmate, J.A., Huycke, M.M., Wilczynski, S., Doroshow, J.H. Cancer Res. (2004) [Pubmed]
  2. Mice with combined disruption of Gpx1 and Gpx2 genes have colitis. Esworthy, R.S., Aranda, R., Martín, M.G., Doroshow, J.H., Binder, S.W., Chu, F.F. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  3. Mutation accumulation in the intestine and colon of mice deficient in two intracellular glutathione peroxidases. Lee, D.H., Esworthy, R.S., Chu, C., Pfeifer, G.P., Chu, F.F. Cancer Res. (2006) [Pubmed]
  4. Glutathione Peroxidase 2, the Major Cigarette Smoke-Inducible Isoform of GPX in Lungs, Is Regulated by Nrf2. Singh, A., Rangasamy, T., Thimmulappa, R.K., Lee, H., Osburn, W.O., Brigelius-Floh??, R., Kensler, T.W., Yamamoto, M., Biswal, S. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  5. Epithelium-specific glutathione peroxidase, Gpx2, is involved in the prevention of intestinal inflammation in selenium-deficient mice. Esworthy, R.S., Yang, L., Frankel, P.H., Chu, F.F. J. Nutr. (2005) [Pubmed]
  6. Genomic analysis of murine pulmonary tissue following carbonyl chloride inhalation. Sciuto, A.M., Phillips, C.S., Orzolek, L.D., Hege, A.I., Moran, T.S., Dillman, J.F. Chem. Res. Toxicol. (2005) [Pubmed]
  7. Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts from gamma-irradiation damage. Esworthy, R.S., Mann, J.R., Sam, M., Chu, F.F. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
  8. Cloning and mapping of the mouse Gpx2 gene encoding gastrointestinal glutathione peroxidase. Tsuji, T., Watanabe, Y., Katoh, H., Sato, K., Kunieda, T. J. Vet. Med. Sci. (1998) [Pubmed]
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