Do goats without prion protein develop chronic demyelinating neuropathy?
Giulia Malachin1, Fredrik Skedsmo1, Birgit Ranheim1, Cecilie Ersdal1, Øyvind Salvesen1, Gjermund Gunnes1, Maren K. Bakkebø1, Malin R. Reiten2, Michael A. Tranulis1, Arild Espenes1
1Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway; 2Norwegian Veterinary Institute, Norway
A unique line of Norwegian dairy goats carries a nonsense mutation that abolish synthesis of the prion protein (PrP). Animals homozygous for this mutation are the only non-transgenic “PrP knockouts” known. PrP has a pivotal role in the development of neurodegenerative prion diseases, such as Creutzfeldt Jakob disease in humans, scrapie in small ruminants and chronic wasting disease in cervids. Initially, the only major phenotype observed in mice with ablation of the PrP gene was complete prion disease resistance. Otherwise, the animals developed normally with normal life expectancies. Subsequent studies have however identified several less obvious abnormalities, tentatively classified as loss of PrP phenotypes. In a series of recent studies, we have investigated responses to lack of PrP in goats. These animals develop and behave normally. Detailed studies, also including that of severe inflammatory stress have however pointed to a modulatory role for PrP in innate immunity signaling, involving type I interferons. One distinct phenotype seen in some lines of PrP knockout mice is a progressive demyelinating neuropathy, affecting peripheral nerves. Further investigations of this condition identified a role for PrP in juxtacrine communication between axons and myelinating Schwann cells, important for myelin maintenance. Intriguingly, we have not observed any clinical evidence of peripheral neuropathy in goats without PrP. We will report clinical and electrophysiological analysis of goats, up to seven years old, without expression of PrP, as well as morphological analysis of peripheral nerves, searching for signs of a sub-clinical imbalance in myelin maintenance.