Demyelinating polyneuropathy in goats lacking prion protein

Studies in mice with ablation of Prnp, the gene that encodes the cellular prion protein (PrP^C ), have led to the hypothesis that PrP^C is important for peripheral nerve myelin maintenance. Here, we have used a nontransgenic animal model to put this idea to the test; namely, goats that, due to a naturally occurring nonsense mutation, lack PrP^C . Teased nerve fiber preparation revealed a demyelinating pathology in goats without PrP^C . Affected nerves were invaded by macrophages and T cells and displayed vacuolated fibers, shrunken axons, and onion bulbs. Peripheral nerve lipid composition was similar in young goats with or without PrP^C , but markedly different between corresponding groups of adult goats, reflecting the progressive nature of the neuropathy. This is the first report of a subclinical demyelinating polyneuropathy caused by loss of PrP^C function in a nontransgenic mammal.