The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells.

The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells.
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DOI:
10.1084/jem.167.2.353
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发表时间:
1988-02-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Adams JM
Adams JM
中科院分区:
其他
文献类型:
--
作者:
Harris AW;Pinkert CA;Crawford M;Langdon WY;Brinster RL;Adams JM

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由IgH增强子(E mu-myc)驱动的c-myc基因转基因小鼠几乎总是发生淋巴瘤,90%在生命的前5个月死亡。肿瘤通常表现为快速进展的淋巴结病,胸腺受累,移植试验显示高度恶性。形态学上,它们是淋巴母细胞性淋巴瘤,通常伴有淋巴样白血病和粒细胞增多症,与37%具有相同(C57 BL/6 x SJL)F2遗传背景的非转基因小鼠中较晚出现的肿瘤不同。31例E mu-myc肿瘤的细胞表面标记物鉴定出52%为前B淋巴瘤,29%为混合前B和B淋巴瘤,19%为B淋巴瘤。这些肿瘤似乎是随机产生于通过myc转基因的组成性表达而扩增的前B细胞群。大多数动物以每周17%的速率开始恶性肿瘤。循环的良性前B细胞自发转化为恶性的速率估计为每代每个细胞约10(-10)。在年轻的E mu-myc小鼠中鉴定的瞬时白细胞增多被开发成用于转基因遗传的快速测定。
Mice transgenic for a c-myc gene driven by the IgH enhancer (E mu-myc) were shown to almost invariably develop lymphomas, 90% succumbing in the first 5 mo of life. The tumors typically presented as rapidly progressive lymphadenopathy with thymic involvement and were highly malignant by transplantation assay. Morphologically, they were lymphoblastic lymphomas, usually accompanied by lymphoid leukemia and granulocytosis, and were distinct from the tumors that arose much later in 37% of nontransgenic mice of the same (C57BL/6 x SJL)F2 genetic background. Cell-surface markers on 31 E mu-myc tumors identified 52% as pre-B lymphomas, 29% as mixed pre-B and B lymphomas, and 19% as B lymphomas. The tumors appeared to arise at random from a population of pre-B cells expanded by constitutive expression of the myc transgene. A majority of the animals initiated malignancy at the rate of 17% per week. The rate at which the cycling, benign pre-B cells spontaneously convert to malignancy was estimated to about 10(-10) per cell per generation. A transient leukocytosis identified in young E mu-myc mice was developed into a rapid assay for inheritance of the transgene.