ISOLATION AND CHARACTERIZATION OF SCHWANN-CELLS FROM NEUROFIBROMATOSIS TYPE-2 PATIENTS

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease of the nervous system characterized by multiple schwannomas. The NF2 gene pr oduct, termed schwannomin or merlin, was hypothesized to function as a cytoskeleton-membrane linking protein due to homology to members of t he protein 4.1 superfamily and to function as a tumor suppressor. We i solated and characterized pure Schwann cell cultures from schwannomas derived from neurofibromatosis 2 patients with identified germline mut ations and loss of heterozygosity. We describe striking differences be tween NF2 and control Schwann cells in morphology, cell-cell contacts, and growth. NF2 Schwann cells form multiple long processes with filop odial and lamellopodial extensions. NF2 Schwann cells lack contact inh ibition, grow in multiple layers, and show a higher proliferation rate than control cells. For the first time Schwann cells derived from pat ients with the NF2 genotype were cultured and characterized in vitro. These cultures are highly valuable for investigating the effects of NF 2 mutations and the development of therapies. (C) 1998 Academic Press.