Truncated prion protein and Doppel are myelinotoxic in the absence of oligodendrocytic PrPC
Truncated prion protein and Doppel are myelinotoxic in the absence of oligodendrocytic PrPC
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DOI：
10.1523/jneurosci.0328-05.2005
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发表时间：
2005-05-11
影响因子：
5.3
通讯作者：
Aguzzi, A
中科院分区：
文献类型：
--
作者：
Radovanovic, I;Braun, N;Aguzzi, A
The cellular prion protein PrPC confers susceptibility to transmissible spongiform encephalopathies, yet its normal function is unknown. Although PrPC- deficient mice develop and live normally, expression of amino proximally truncated PrPC (Delta PrP) or of its structural homolog Doppel ( Dpl) causes cerebellar degeneration that is prevented by coexpression of full- length PrPC. We now report that mice expressing Delta PrP or Dpl suffer from widespread leukoencephalopathy. Oligodendrocyte- specific expression of full- length PrPC 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 PrPC expression under control of the neuron- specific enolase ( NSE) promoter antagonized CGC degeneration but not leukoencephalopathy. PrPC 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 PrPC in myelin maintenance.
