| First Author | Li A | Year | 2007 |
| Journal | EMBO J | Volume | 26 |
| Issue | 2 | Pages | 548-58 |
| PubMed ID | 17245437 | Mgi Jnum | J:117788 |
| Mgi Id | MGI:3697579 | Doi | 10.1038/sj.emboj.7601507 |
| Citation | Li A, et al. (2007) Neonatal lethality in transgenic mice expressing prion protein with a deletion of residues 105-125. EMBO J 26(2):548-58 |
| abstractText | To identify sequence domains important for the neurotoxic and neuroprotective activities of the prion protein (PrP), we have engineered transgenic mice that express a form of murine PrP deleted for a conserved block of 21 amino acids (residues 105-125) in the unstructured, N-terminal tail of the protein. These mice spontaneously developed a severe neurodegenerative illness that was lethal within 1 week of birth in the absence of endogenous PrP. This phenotype was reversed in a dose-dependent fashion by coexpression of wild-type PrP, with five-fold overexpression delaying death beyond 1 year. The phenotype of Tg(PrPDelta105-125) mice is reminiscent of, but much more severe than, those described in mice that express PrP harboring larger deletions of the N-terminus, and in mice that ectopically express Doppel, a PrP paralog, in the CNS. The dramatically increased toxicity of PrPDelta105-125 is most consistent with a model in which this protein has greatly enhanced affinity for a hypothetical receptor that serves to transduce the toxic signal. We speculate that altered binding interactions involving the 105-125 region of PrP may also play a role in generating neurotoxic signals during prion infection. |
