• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

EMBO J 2007 Jun 6;26(11):2777-85

Prion protein with an octapeptide insertion has impaired neuroprotective activity in transgenic mice.

Li A, Piccardo P, Barmada SJ, Ghetti B, Harris DA

Harris DA (reprint author), Washington Univ, Sch Med, Dept Cell Biol & Physiol, 660 S Euclid Ave, St Louis, MO 63110 USA Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA Indiana Univ, Sch Med, Div Neuropathol, Indianapolis, IN 46204 USA US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA


Familial prion diseases are due to dominantly inherited, germline mutations in the PRNP gene that encodes the prion protein (PrP). The cellular mechanism underlying the pathogenic effect of these mutations remains uncertain. To investigate whether pathogenic mutations impair a normal, physiological activity of PrP, we have crossed Tg(PG14) mice, which express PrP with an octapeptide insertion associated with an inherited prion dementia, with Tg(PrPDelta32-134) mice. Tg(PrPDelta32-134) mice, which express an N-terminally truncated form of PrP, spontaneously develop a neurodegenerative phenotype that is stoichiometrically reversed by coexpression of wild-type PrP. We find that, at equivalent expression levels, PG14 PrP is significantly less efficient than wild-type PrP in suppressing the development of clinical symptoms and neuropathology in Tg(PrPDelta32-134) mice. Thus, our results suggest that some features of the neurological illness associated with inherited PrP mutations may be attributable to a loss of PrP neuroprotective function. This mechanism stands in contrast to the toxic gain-of-function mechanisms that are usually invoked to explain the pathogenesis of dominantly inherited neurodegenerative disorders.

Category: Journal Article
PubMed ID: #17510630
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29