Induction of HO-1 and NOS in doppel-expressing mice devoid of PrP: Implications for doppel function

Academic Article


  • Ectopic expression of the doppel (Dpl) protein, a homologue of the prion protein (PrP), was recently associated with cerebellar Purkinje cell degeneration observed in two aging prion protein knock-out (Prnp0/0) mouse lines. We investigated the possible role of Dpl in oxidative metabolism. Two Prnp0/0 mouse lines of similar genetic background were studied. One line expresses Dpl in the brain and displays Dpl-associated cerebellar abnormalities. The other has no elevated expression of Dpl and no cerebellar abnormalities. We observed a correlation between Dpl expression and the induction of both heme oxygenase 1 (HO-1) and nitric oxide synthase systems (nNOS and iNOS). These responses are suggestive of increased oxidative stress in the brains of the Dpl-expressing Prnp0/0 mice. No induction was observed with Hsp-60, indicating a specific response by the HO/NOS system. We proposed that Dpl expression exacerbates oxidative damage that is antagonistic to the protective function of wild-type PrP.
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    Author List

  • Wong BS; Liu T; Paisley D; Li R; Pan T; Chen SG; Perry G; Petersen RB; Smith MA; Melton DW
  • Start Page

  • 768
  • End Page

  • 775
  • Volume

  • 17
  • Issue

  • 4