Lethal recessive myelin toxicity of prion protein lacking its central domain

Frank Baumann, Markus Tolnay, Christine Brabeck, Jens Pahnke, Ulrich Kloz, Hartmut H. Niemann, Mathias Heikenwalder, Thomas Rülicke, Alexander Bürkle, Adriano Aguzzi*

*Corresponding author for this work
181 Citations (Scopus)


PrPC-deficient mice expressing prion protein variants with large amino-proximal deletions (termed PrPΔF) suffer from neurodegeneration, which is rescued by full-length PrPC. We now report that expression of PrPΔCD, a PrP variant lacking 40 central residues (94-134), induces a rapidly progressive, lethal phenotype with extensive central and peripheral myelin degeneration. This phenotype was rescued dose-dependently by coexpression of full-length PrPC or PrP C lacking all octarepeats. Expression of a PrPC variant lacking eight residues (114-121) was innocuous in the presence or absence of full-length PrPC, yet enhanced the toxicity of PrP ΔCD and diminished that of PrPΔF. Therefore, deletion of the entire central domain generates a strong recessive-negative mutant of PrPC, whereas removal of residues 114-121 creates a partial agonist with context-dependent action. These findings suggest that myelin integrity is maintained by a constitutively active neurotrophic protein complex involving PrPC, whose effector domain encompasses residues 94-134.

Original languageEnglish
JournalEMBO Journal
Issue number2
Pages (from-to)538-547
Number of pages10
Publication statusPublished - 24.01.2007

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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