PMP22 transgenic dorsal root ganglia cultures show myelin abnormalities similar to those of human CMT1A

Charcot-Marie-Tooth 1A (CMT1A) neuropathy is caused by duplication of the p eripheral myelin protein 22 (PMP22) gene, leading to protein overexpression . Although this protein has a role in regulating Schwann cell growth and pe ripheral myelin compaction, how altered concentrations of PMP22 impair myel ination is unknown. We established dorsal root ganglia (DRG) cultures from a transgenic rat overexpressing PMP22 (PMP22(tg)) to study the behavior of PMP22(tg) Schwann cells in early stages of development and myelination. We used reverse transcriptase-polymerase chain reaction and light and electron microscopy to study PMP22 expression and myelin formation. Myelin ultrastr ucture was evaluated in sural nerves from CMT1A patients to compare experim ental and human findings. PMP22(tg) DRG cultures contained a greater number of internodes devoid of myelin, in the absence of remyelination, and incre ased periodicity of myelin lamellae compared with normal cultures. Widening of myelin lamellae was also observed in CMT1A biopsy specimens, Our result s suggest that both functions of PMP22, in regulating Schwann cell differen tiation and contributing to peripheral myelin compaction, are affected by i ts overexpression, The presence of similar myelin abnormalities in PMP22(tg ) cultures and human nerves emphasizes the importance of developing in vitr o models of hereditary neuropathies to study their underlying pathomechanis ms.