DYSTONIN IS AN ESSENTIAL COMPONENT OF THE SCHWANN-CELL CYTOSKELETON AT THE TIME OF MYELINATION

A central role for the Schwann cell cytoskeleton in the process of per ipheral nerve myelination has long been suggested, However, there is n o genetic or biological evidence as yet to support this assumption. He re we show that dystonia musculorum (dt) mice, which carry mutations i n dystonin, a cytoskeletal crosslinker protein, have hypo/amyelinated peripheral nerves. In neonatal df mice, Schwann cells were arrested at the promyelinating stage and had multiple myelinating lips. Nerve gra ft experiments and primary cultures of Schwann cells demonstrated that the myelination abnormality in dt mice was autonomous to Schwann cell s. In culture, dt Schwann cells showed abnormal polarization and matri x attachment, and had a disorganized cytoskeleton, Finally, we show th at the dt mutation was semi-dominant, heterozygous animals presenting hypo- and hyper-myelinated peripheral nerves, Altogether, our results suggest that dt Schwann cells are deficient for basement membrane inte raction and demonstrate that dystonin is an essential component of the Schwann cell cytoskeleton at the time of myelination.