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Title: Behavioral abnormalities in prion protein knockout mice and the potential relevance of PrPc for the cytoskeleton

item SCHMITZ, MATTHIAS - Georg August University
item ZAFAR, SAIMA - Georg August University
item Silva, Christopher - Chris
item ZERR, INGA - Georg August University

Submitted to: Prion
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/26/2014
Publication Date: 11/2/2014
Publication URL:
Citation: Schmitz, M., Zafar, S., Silva, C.J., Zerr, I. 2014. Behavioral abnormalities in prion protein knockout mice and the potential relevance of PrPc for the cytoskeleton. Prion. 8(6) 381-386.

Interpretive Summary: All mammals possess a nearly identical normal cellular prion protein. The fact that it is so similar in all mammals suggests that it plays some crucial role in an animal’s life. Although it has been studied, its exact role is still not clear. Animals that do not produce the normal cellular prion protein seem to be normal. Transgenic mice that are engineered to not produce a normal cellular prion protein have been used to study the role of this protein. These animals show subtle deficits in behavior, such as difficulty in learning, greater anxiety, and a marked inability to build nests. With the exception of nest building, these behavioral changes become more pronounced as the animals age. We determined the molecular basis of these behavioral deficits was related to the proteins that make up the cytoskeleton. The normal cellular prion protein plays an important role in regulating the movement of the proteins that build and maintain the cytoskeleton.

Technical Abstract: The cellular prion protein (PrPC) is a highly conserved protein, which is anchored to the outer surface of the plasma membrane. Even though its physiological function has already been investigated in different cell or mouse models where PrPC expression is either up-regulated or depleted, its exact physiological role in a mammalian organism remains elusive. Recent studies indicate that PrPC has multiple functions and is involved in cognition, learning, anxiety, locomotion, depression, offensive aggression and nest building behavior. While young animals (3 months of age) show only marginal abnormalities, most of the deficits become apparent as the animals age, which might indicate its role in neurodegeneration or neuroprotection. However, the exact biochemical mechanism and signal transduction pathways involving PrPC are only slowly becoming clearer. We report the observations made in different studies using different Prnp0/0 mouse models and propose that PrPC plays an important role in the regulation of cytoskeletal proteins.