The physiological role of prion protein (PrP) remains unknown. Mice devoid of PrP develop normally but are resistant to scrapie; introduction of a PrP transgene restores susceptibility to the disease. To identify the regions of PrP necessary for this activity, we prepared PrP knockout mice expressing PrPs with amino-proximal deletions. Surprisingly, PrP lacking residues 32121 or 32-134, but not with shorter deletions, caused severe ataxia and neuronal death limited to the granular layer of the cerebellum as early as 1-3 months after birth. The defect was completely abolished by introducing one copy of a wild-type PrP gene. We speculate that these truncated PrPs may be nonfunctional and compete with some other molecule with a PrP-like function for a common ligand.
Shmerling, D., Hegyi, I., Fischer, M., Blättler, T., Brandner, S., Götz, J., … Weissmann, C. (1998). Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell, 93(2), 203–214. https://doi.org/10.1016/S0092-8674(00)81572-X