Green J E, Baird A M, Hinrichs S H, Klintworth G K, Jay G
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702-1201.
Am J Pathol. 1992 Jun;140(6):1401-10.
The expression of the human T-cell lymphotropic virus type 1 (HTLV-1) tax gene in transgenic mice has been shown to result in the development of neurofibromas. Further characterization of these transgenic mice has revealed other significant pathologic similarities between this transgenic mouse model and human neurofibromatosis (NF). Pheochromocytomas of the adrenal medulla and hamartomas of the iris are well-recognized manifestations of human NF. Adrenal medullary tumors have been found in 68% of transgenic animals that were studied. They appear, however, not to be pheochromocytomas, but rather composed of undifferentiated spindle cells. Proliferation of fibroblastlike cells in the iris also occurs in one-half of the transgenic animals surviving more than 6 months. Melanocytes, however, have not been found in the transgenic iris lesion, although they are characteristically found in the Lisch nodules of human NF. The similarities between human neurofibromatosis and this transgenic mouse model (in which the overexpression of a single gene results in neoplasia) are discussed. This transgenic system may provide further insights into molecular mechanisms involved in the pathogenesis of neurofibromatosis.
已证明人类1型嗜T细胞淋巴细胞病毒（HTLV-1）tax基因在转基因小鼠中的表达会导致神经纤维瘤的发生。对这些转基因小鼠的进一步研究表明，该转基因小鼠模型与人类神经纤维瘤病（NF）之间存在其他显著的病理相似性。肾上腺髓质嗜铬细胞瘤和虹膜错构瘤是人类NF的公认表现。在所研究的转基因动物中，68%发现有肾上腺髓质肿瘤。然而，它们似乎不是嗜铬细胞瘤，而是由未分化的梭形细胞组成。存活超过6个月的转基因动物中有一半在虹膜中也出现了成纤维细胞样细胞的增殖。不过，在转基因虹膜病变中未发现黑素细胞，而黑素细胞在人类NF的Lisch结节中是典型存在的。本文讨论了人类神经纤维瘤病与这种转基因小鼠模型（其中单个基因的过表达导致肿瘤形成）之间的相似性。这个转基因系统可能会为神经纤维瘤病发病机制所涉及的分子机制提供进一步的见解。
