NEUROFIBROMIN-DEFICIENT FIBROBLASTS FAIL TO FORM PERINEURIUM IN-VITRO

To identify cell type(s) that might contribute to nerve sheath tumors (neurofibromas) in patients with neurofibromatosis type 1, we generate d cell cultures. containing neurons, Schwann cells and fibroblasts fro m transgenic mouse embryos in which the type 1 neurofibromatosis gene was disrupted by homologous recombination (Brannan et al. (1994) Genes Development, 8,1019-1029). Normal fascicle formation by perineurial c ells failed to occur in the absence of neurofibromin. Fascicles were r educed in number and showed abnormal morphology when normal neurons an d Schwann cells were cultured up to 37 days with fibroblasts lacking n eurofibromin. Proliferation was increased in a majority of fibroblast cell strains analyzed from embryos lacking neurofibromin. These observ ations suggest that mutations in the neurofibromatosis type 1 gene aff ect fibroblast behavior that might contribute to neurofibroma formatio n in patients with neurofibromatosis type 1.