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

• We can conclude that the Gpx2 gene compensates for the lack of Gpx1 gene expression in the ileal epithelium [7].
• The nucleotide sequence of the pseudogene was 98.3% identical with that of the mouse Gpx2 gene and showed characteristics of a processed pseudogene [8].

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].

References