Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunumcrypts from gamma-irradiation damage

Gpx1 knockout (KO) mice had a higher number of regenerating crypts in the j ejunum than did Gpx2-KO or wild-type mice analyzed 4 days after greater tha n or equal to 10 Gy gamma-irradiation. Without gamma-irradiation, glutathio ne peroxidase (GPX) activity in the jejunal and ileal epithelium of Gpx1-KO mice was <10 and similar to 35%, respectively, of that of the wild-type mi ce. Four days after exposure to 11 Gy, GPX activity in wild-type and Gpx1-K O ileum was doubled and tripled, respectively. However, jejunal GPX activit y was not changed. Thus the lack of GPX activity in the jejunum is associat ed with better regeneration of crypt epithelium after radiation. Gpx2 gene expression was solely responsible for the increase in GPX activity in the i leum, since radiation did not alter GPX activity in Gpx2-KO mice. The intes tinal Gpx2 mRNA levels of Gpx1-KO and wild-type mice increased up to 14- an d 7-fold after radiation, respectively. Although the Gpx1-KO jejunum had hi gher levels of PGE(2) than the wild-type jejunum after exposure to 0 or 15 Gy, these differences were not statistically significant. Thus whether GPX inhibits PG biosynthesis in vivo remains to be established. We can conclude that the Gpx2 gene compensates for the lack of Gpx1 gene expression in the ileal epithelium. This may have abolished the protective effect in Gpx1-KO mice against the radiation damage in the ileum.