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 Pr (c) function in a nontransgenic mammal.