Myelin, the axon insulator needed for effective action potential propagation, breaks down in several neurological diseases, most notably multiple sclerosis (MS). Patients afflicted with MS suffer progressive deficits in balance, coordination and movement, as well as visual and sensory disturbances. Here, Abdiwahab Musse and colleagues report on a mouse model of demyelinating disease created through overexpression of peptidylarginine deiminase 2 (PAD2), an enzyme which converts peptide-bound arginine, a positively charged amino acid, into citrulline, a neutral amino acid, in myelin basic protein. The PAD2-overexpressing mice had white matter lesions as well as nude and hypomyelinated axons. Behavioral analysis showed that, like MS patients, the mice also had abnormal movement, balance and coordination. The authors’ work presented here highlights the importance of PAD2 regulation in myelin stability, and presents a new animal model for demyelinating disease.
