Murine prions transferred from brain to cultured cells gradually adapt to the new environment. Brain‐derived 22L prions can infect neuroblastoma‐derived PK1 cells in the presence of swainsonine (swa); that is, they are ‘swa resistant’. PK1 cell‐adapted 22L prions are swa sensitive; however, propagation in swa results in selection of swa‐resistant substrains. Cloned, PK1 cell‐adapted 22L prions were initially unable to develop swa resistance (‘swa incompetent’); however, after serial propagation for 30–90 doublings, four of nine clones became swa competent, showing that swa‐resistant ‘mutants’ arose during replication. Mutations in the case of prions are attributed to heritable changes in PrPSc conformation. One clone remained swa incompetent even after 1035‐fold expansion; surprisingly, after propagation in brain, it yielded swa‐resistant prions, indistinguishable from the original 22L population. Thus, cell‐adapted 22L prions assumed either mutable or virtually immutable conformations; however, when passaged through the brain all became mutable. Mutability is thus a substrain‐specific attribute.
- Received June 15, 2011.
- Revision received September 6, 2011.
- Accepted September 8, 2011.
- Copyright © 2011 European Molecular Biology Organization
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