Rosenbaum T, Boissy Y L, Kombrinck K, Brannan C I, Jenkins N A, Copeland N G, Ratner N
Department of Cell Biology, University of Cincinnati College of Medicine, Ohio 45267-0521, USA.
Development. 1995 Nov;121(11):3583-92. doi: 10.1242/dev.121.11.3583.
To identify cell type(s) that might contribute to nerve sheath tumors (neurofibromas) in patients with neurofibromatosis type 1, we generated cell cultures containing neurons. Schwann cells and fibroblasts from 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 cells failed to occur in the absence of neurofibromin. Fascicles were reduced in number and showed abnormal morphology when normal neurons and Schwann cells were cultured up to 37 days with fibroblasts lacking neurofibromin. Proliferation was increased in a majority of fibroblast cell strains analyzed from embryos lacking neurofibromin. These observations suggest that mutations in the neurofibromatosis type I gene affect fibroblast behavior that might contribute to neurofibroma formation in patients with neurofibromatosis type 1.
为了确定可能导致1型神经纤维瘤病患者神经鞘瘤（神经纤维瘤）的细胞类型，我们培养了含有神经元、雪旺细胞和成纤维细胞的细胞培养物，这些细胞来自通过同源重组破坏了1型神经纤维瘤病基因的转基因小鼠胚胎（布兰南等人，《基因与发育》，1994年，第8卷，第1019 - 1029页）。在缺乏神经纤维瘤蛋白的情况下，神经束膜细胞无法形成正常的束状结构。当正常神经元和雪旺细胞与缺乏神经纤维瘤蛋白的成纤维细胞一起培养37天时，束状结构数量减少且形态异常。在分析的大多数来自缺乏神经纤维瘤蛋白胚胎的成纤维细胞系中，细胞增殖增加。这些观察结果表明，1型神经纤维瘤病基因的突变会影响成纤维细胞的行为，这可能导致1型神经纤维瘤病患者形成神经纤维瘤。
