Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-60830
Steele, A D; Lindquist, S; Aguzzi, A (2007). The prion protein knockout mouse: a phenotype under challenge. Prion, 1(2):83-93.
The key pathogenic event in prion disease involves misfolding and aggregation of the cellular prion protein (PrP). Beyond this fundamental observation, the mechanism by which PrP misfolding in neurons leads to injury and death remains enigmatic. Prion toxicity may come about by perverting the normal function of PrP. If so, understanding the normal function of PrP may help to elucidate the molecular mechansim of prion disease. Ablation of the Prnp gene, which encodes PrP, was instrumental for determining that the continuous production of PrP is essential for replicating prion infectivity. Since the structure of PrP has not provided any hints to its possible function, and there is no obvious phenotype in PrP KO mice, studies of PrP function have often relied on intuition and serendipity. Here, we enumerate the multitude of phenotypes described in PrP deficient mice, many of which manifest themselves only upon physiological challenge. We discuss the pleiotropic phenotypes of PrP deficient mice in relation to the possible normal function of PrP. The critical question remains open: which of these phenotypes are primary effects of PrP deletion and what do they tell us about the function of PrP?
|Item Type:||Journal Article, refereed, further contribution|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|DDC:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||02 Jul 2012 15:09|
|Last Modified:||05 Dec 2013 23:07|
|Citations:||Web of Science®. Times Cited: 46|
Scopus®. Citation Count: 49
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