Differential expression of cellular prion protein in mouse brain as detected with multiple anti-PrP monoclonal antibodies

The normal cellular prion protein (PrPC) plays an essential role in the development of prion diseases. Indirect evidence has suggested that different PrPC glycoforms may be expressed in different brain regions and perform distinct functions. However, due to a lack of monoclonal antibodies (Mabs) that are specific for mouse PrPC, the expression of PrPC in the mouse brain has not been studied in great detail. We used Mabs specific for either the N-terminus or the C-terminus of the mouse PrPC to study its expression in the mouse brain by immunoblotting and immunohistochemistry. Immunoblotting studies demonstrated that the expression of PrPC differed quantitatively as well as qualitatively in different regions of the brain. The anti-C-terminus Mabs reacted with all three molecular weight bands of PrPC; the anti-N-terminus Mabs only reacted with the 39-42 kDa PrPC. The results from immunohistochemical staining revealed the spatial distribution of PrPC in the mouse brain, which were consistent with that from immunoblotting. Although expression of PrPC has been reported to be required for long-term survival of Purkinje cells, we were unable to detect PrPC in the Purkinje cell layer in the cerebellum with multiple anti-PrP Mabs. Our findings suggest that PrPC variants, i.e. various glycoforms and truncated forms, might be specifically expressed in different regions of mouse brain and might have different functions. (C) 2001 Elsevier Science B.V. All rights reserved.