Behavioral abnormalities in prion protein knockout mice and the potential relevance of PrPC for the cytoskeleton |
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Authors: | Matthias Schmitz Saima Zafar Christopher J Silva Inga Zerr |
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Institution: | 1.Department of Neurology; University Medical Center Göttingen, and German Center for Neurodegenerative Diseases (DZNE); Göttingen, Germany;2.USDA, Produce Safety & Microbiology Research Unit; Western Regional Research Center; Albany, CA USA |
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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 upregulated 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 gradually 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 the cytoskeleton and associated proteins. In particular, we showed a nocodazole treatment influenced colocalization of PrPC and α tubulin 1. In addition, we confirmed the observed deficits in nest building using a different backcrossed Prnp0/0 mouse line. |
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Keywords: | aging behavior cellular prion protein cytoskeleton tubulin |
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