Age‐dependent neuromuscular impairment in prion protein knockout mice

: The cellular prion protein (PrP C ) is commonly recognized as the precursor of prions, the infectious agents of the fatal transmissible spongiform encephalopathies, or prion diseases. Despite extensive effort, the physiological role of PrP C is still ambiguous. Evidence has suggested that PrP C is involved in different cellular functions, including peripheral nerve integrity and skeletal muscle physiology . Methods : We analyzed the age‐dependent influence of PrP C on treadmill test–based aerobic exercise capacity and on a series of morphological and metabolic parameters using wild‐type and genetically modified mice of different ages expressing, or knockout (KO) for, PrP C . Results : We found that aged PrP‐KO mice displayed a reduction in treadmill performance compared with PrP‐expressing animals, which was associated with peripheral nerve demyelination and alterations of skeletal muscle fiber type. Conclusion : PrP‐KO mice have an age‐dependent impairment of aerobic performance as a consequence of specific peripheral nerve and muscle alterations. Muscle Nerve 53: 269–279, 2016