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

Boon Seng Wong, Tong Liu, Derek Paisley, Ruliang Li, Tao Pan, Shu G. Chen, George Perry, Robert B. Petersen, Mark A. Smith, David W. Melton, Pierluigi Gambetti, David R. Brown, Man Sun Sy

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61 Scopus citations


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.

Original languageEnglish
Pages (from-to)768-775
Number of pages8
JournalMolecular and Cellular Neuroscience
Issue number4
StatePublished - 2001


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