Schmidt E V, Pattengale P K, Weir L, Leder P
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1988 Aug;85(16):6047-51. doi: 10.1073/pnas.85.16.6047.
Transgenic mice carrying a fusion gene in which the mouse immunoglobulin enhancer has been inserted into an otherwise normal human c-myc gene develop a narrow spectrum of pre-B-cell lymphomas. Tumor occurrence is correlated with expression of the transgene in organs in which large numbers of pre-B cells predominate. These tumors, which arise stochastically, are virtually all lymphoblastic lymphomas of the pre-B-cell type. Evidently the isolated enhancer targets oncogene expression and tumorigenesis to the early B-cell population in preference to more mature B-cell populations. The transgene also confers enhanced in vitro growth properties on nontransformed pre-B cells as observed in bone marrow cultures derived from transgenic animals. These cultured cells represent a population in which the activating function of c-myc can be uncoupled from secondary oncogenic events occurring in vivo.
携带融合基因的转基因小鼠，该融合基因是将小鼠免疫球蛋白增强子插入到一个原本正常的人类c-myc基因中，会发生范围较窄的前B细胞淋巴瘤。肿瘤的发生与转基因在大量前B细胞占主导的器官中的表达相关。这些随机发生的肿瘤实际上都是前B细胞型的淋巴母细胞淋巴瘤。显然，分离出的增强子优先将癌基因表达和肿瘤发生靶向早期B细胞群体，而非更成熟的B细胞群体。如在源自转基因动物的骨髓培养物中所观察到的，转基因还赋予未转化的前B细胞增强的体外生长特性。这些培养细胞代表了一个群体，其中c-myc的激活功能可以与体内发生的继发性致癌事件解耦联。
