IMPROVED CULTURE METHODS TO EXPAND SCHWANN-CELLS WITH ALTERED GROWTH-BEHAVIOR FROM CMT1A PATIENTS

A duplication of the gene for myelin protein PMP22 is by far the most common cause of the hereditary demyelinating neuropathy CMT1A. A role for PMP22 in cell growth in addition to its function as a myelin prote in has been suggested because PMP22 is homologous to a gene specifical ly upregulated during growth arrest. Furthermore, transfected rat Schw ann cells overexpressing PMP22 show reduced growth. In addition, abnor mal Schwann cell differentiation has been described in nerve biopsies from CMT1A patients. To analyse whether the duplication of the PMP22 g ene in CMT1A neuropathy primarily alters Schwann cell differentiation and to exclude nonspecific secondary responses, we improved human Schw ann cell culturing. This allowed us long-term passaging of human Schwa nn cells with unchanged phenotype, assessed by expression of different Schwann cell markers. Subsequently we established Schwann cell cultur es from CMT1A nerve biopsies. We find decreased proliferation of Schwa nn cells from different CMT1A patients in all passages. We also demons trate PMP22 mRNA overexpression in cultured CMT1A Schwann cells. We co nclude that decreased proliferation in cultured Schwann cells that car ry the CMT1A duplication indicates abnormal differentiation of CMT1A S chwann cells. The identification of an abnormal phenotype of CMT1A Sch wann cells in culture could possibly lead to an in vitro disease model . (C) 1998 Wiley-Liss, Inc.