Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1937
Radovanovic, I; Braun, N; Giger, O T; Mertz, K; Miele, G; Prinz, M; Navarro, B; Aguzzi, A (2005). Truncated prion protein and Doppel are myelinotoxic in the absence of oligodendrocytic PrPC. Journal of Neuroscience, 25(19):4879-4888.
The cellular prion protein PrP(C) confers susceptibility to transmissible spongiform encephalopathies, yet its normal function is unknown. Although PrP(C)-deficient mice develop and live normally, expression of amino proximally truncated PrP(C) (DeltaPrP) or of its structural homolog Doppel (Dpl) causes cerebellar degeneration that is prevented by coexpression of full-length PrP(C). We now report that mice expressing DeltaPrP or Dpl suffer from widespread leukoencephalopathy. Oligodendrocyte-specific expression of full-length PrP(C) under control of the myelin basic protein (MBP) promoter repressed leukoencephalopathy and vastly extended survival but did not prevent cerebellar granule cell (CGC) degeneration. Conversely, neuron-specific PrP(C) expression under control of the neuron-specific enolase (NSE) promoter antagonized CGC degeneration but not leukoencephalopathy. PrP(C) was found in purified myelin and in cultured oligodendrocytes of both wild-type and MBP-PrP transgenic mice but not in NSE-PrP mice. These results identify white-matter damage as an extraneuronal PrP-associated pathology and suggest a previously unrecognized role of PrP(C) in myelin maintenance.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine|
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Date:||11 May 2005|
|Deposited On:||11 Feb 2008 12:26|
|Last Modified:||27 Nov 2013 17:15|
|Publisher:||Society for Neuroscience|
|Citations:||Web of Science®. Times Cited: 55|
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