ONCOGENESIS OF THE LENS IN TRANSGENIC MICE

ONCOGENESIS OF THE LENS IN TRANSGENIC MICE
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DOI:
10.1126/science.3029873
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发表时间:
1987-03-27
期刊:
影响因子:
56.9
通讯作者:
WESTPHAL, H
WESTPHAL, H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
MAHON, KA;CHEPELINSKY, AB;WESTPHAL, H

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脊椎动物的晶状体肿瘤不是自然发生的。携带含有小鼠α的杂交基因的转基因小鼠。a -晶体蛋白启动子(-366 ~ +46)与sv40t抗原编码序列融合形成晶状体肿瘤,使眼腔消失,甚至侵犯邻近组织,从而确定晶状体不是屈光致癌。在晶状体发育早期检测到大t抗原;它引起晶状体纤维细胞的形态改变,并特异性地干扰晶状体纤维细胞的分化。.alpha。-和。beta。-晶体蛋白在许多晶状体肿瘤细胞中持续存在,而。-结晶蛋白被选择性还原。可及性、特征形态和明确的蛋白质标记使这种透明上皮性眼组织成为检测癌基因致瘤性和研究从开始到动物死亡的恶性转化的潜在有用系统。
Neoplastic tumors of the ocular lens of vertebrates do not naturally occur. Transgenic mice carrying a hybrid gene comprising the murine .alpha.A-crystallin promoter (-366 to +46) fused to the coding sequence of the SV40 T antigens developed lens tumors, which obliterated the eye cavity and even invaded neighboring tissue, thus establishing that the lens is not refractive to oncogenesis. Large-T antigen was detected early in lens development; it elicited morphological changes and specifically interfered with differentiation of lens fiber cells. Both .alpha.- and .beta.-crystallins persisted in many of the lens tumor cells, while .gamma.-crystallin was selectively reduced. Accessibility, characteristic morphology, and defined protein markers make this transparent epithelial eye tissue a potentially useful system for testing tumorigenicity of oncogenes and for studying malignant transformation from its inception until death of the animal.