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 dev elopment of prion diseases. Indirect evidence has suggested that different PrPC glycoforms may be expressed in different brain regions and perform dis tinct functions. However, due to a lack of monoclonal antibodies (Mabs) tha t are specific for mouse PrPC, the expression of PrPC in the mouse brain ha s 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 stu dies demonstrated that the expression of PrPC differed quantitatively as we ll 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-term inus Mabs only reacted with the 39-42 kDa PrPC. The results from immunohist ochemical staining revealed the spatial distribution of PrPC in the mouse b rain, which were consistent with that from immunoblotting. Although express ion of PrPC has been reported to be required for long-term survival of Purk inje 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 var iants, i.e. various glycoforms and truncated forms, might be specifically e xpressed in different regions of mouse brain and might have different funct ions. (C) 2001 Elsevier Science B.V. All rights reserved.