Mouse models of tumor development in neurofibromatosis type 1
Mouse models of tumor development in neurofibromatosis type 1
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DOI：
10.1126/science.286.5447.2172
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发表时间：
1999-12-10
期刊：
影响因子：
56.9
通讯作者：
Jacks, T
中科院分区：
文献类型：
--
作者：
Cichowski, K;Shih, TS;Jacks, T
1型神经纤维瘤病(NF1)是一种常见的常见癌症综合征，由NF1抑癌基因的胚系突变引起。本病的显著特征是良性周围神经鞘瘤(神经纤维瘤)的发展，可进展为恶性。与人类不同的是，NF1基因突变杂合子的小鼠不会患上神经纤维瘤。然而，正如这里所描述的，由部分NF1(-/-)细胞组成的嵌合小鼠确实如此，这表明野生型NF1等位基因的丢失在肿瘤形成中是限速的。此外，携带NF1和P53基因连锁胚系突变的小鼠会患上恶性周围神经鞘瘤(MPNSTs)，这支持了P53突变在MPNST发生中的协同和因果作用。这两个小鼠模型提供了解决疾病发展的基本方面和测试：治疗策略的手段。
Neurofibromatosis type 1 (NF1) is a prevalent familiar cancer syndrome resulting from germ Line mutations in the NF1 tumor suppressor gene. Hallmark features of the disease are the development of benign peripheral nerve sheath tumors (neurofibromas), which can progress to malignancy. Unlike humans, mice that are heterozygous for a mutation in Nf1 do not develop neurofibromas. However, as described here, chimeric mice composed in part of Nf1(-/-) cells do, which demonstrates that loss of the wild-type Nf1 allele is rate-limiting in tumor formation. In addition, mice that carry Linked germ line mutations in Nf1 and p53 develop malignant peripheral nerve sheath tumors (MPNSTs), which supports a cooperative and causal role for p53 mutations in MPNST development. These two mouse models provide the means to address fundamental aspects of disease development and to test: therapeutic strategies.