Development of heritable melanoma in transgenic mice
Development of heritable melanoma in transgenic mice
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DOI：
10.1046/j.1523-1747.1998.00133.x
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发表时间：
1998-03-01
影响因子：
6.5
通讯作者：
Chen, SZ
中科院分区：
文献类型：
--
作者：
Zhu, H;Reuhl, K;Chen, SZ
通过转染将遗传物质转移到受体细胞中已成功地用于分离负责特定表型性状的基因。通过使用这种策略，分离DNA片段，当转染到适当的未定型细胞中时，将使受体细胞进行脂肪细胞分化。用活性DNA克隆之一克隆B产生转基因小鼠。预期转基因小鼠将显示脂肪细胞相关表型;然而，这些动物在年轻时就产生了含有黑色素的肿瘤。将克隆B插入小鼠DNA中可能中断了参与细胞生长调节的基因，特别是黑色素产生细胞中细胞生长的调节。对这些小鼠的组织学分析显示，早在10 - 12日龄时，动物的耳垂上就有黑点。到3个月时，除耳垂外，在其他器官中可观察到色素瘤。这些转基因小鼠中有相当数量在1岁内死亡。在没有任何已知的化学致癌物或紫外线辐射的情况下，这些动物的黑色素瘤自发发展。这一品系的小鼠提供了一种鉴定参与细胞生长控制和分化调节的基因的方法。这些小鼠也可作为研究黑色素瘤的分子、遗传和表型特征和发展的模型系统。
Transfer of genetic material into recipient cells by transfection has been used successfully to isolate genes responsible for particular phenotypic traits. By using this strategy, DNA fragments were isolated that when transfected into appropriate uncommitted cells will commit the recipient cells to undergo adipocyte differentiation. Transgenic mice were generated with one of the active DNA clones, Clone B. The transgenic mice were expected to display an adipocyte-related phenotype; however, the animals developed melanin containing tumors at a young age. Insertion of Clone B into the mouse DNA probably interrupted a gene(s) that is involved in the regulation of cell growth, specifically regulation of cell growth in melanin-producing cells. Histopathologic analysis of these mice showed dark spots on the ear lobes of the animals as early as 10-12 d of age. By 3 mo, in addition to the ear lobes, pigmented tumors could be observed in other organs. A significant number of these transgenic mice died within 1 y of age. The melanomas developed spontaneously in these animals in the absence of any known chemical carcinogen or ultraviolet radiation. This line of mice provides a way of identifying genes involved in regulation of cell growth control and differentiation. These mice also serve as a model system to investigate the molecular, genetic, and phenotypic characterization and development of melanomas.