突变Myc基因骨髓特异性转基因小鼠肿瘤模型的建立及鉴定

目的 研究通过外源Myc基因转染造血细胞,实现骨髓特异性转基因并形成淋巴瘤的潜能.方法 造血细胞转染野生型与突变型Myc基因.移植入经~(60)Coγ射线照射的C57BL/6小鼠,观察小鼠形成肿瘤时间以及小鼠自然死亡时间,免疫组织化学染色法检测肿瘤类型;流式细胞术检测外源Myc基因在小鼠骨髓MNC中的表达;骨髓造血细胞、肝、脾、肿瘤组织行Myc免疫印迹法检测Myc在体内的表达情况.结果 Mye基因转基因后形成B细胞淋巴瘤,流式细胞术检测发现外源Myc基因可在造血细胞表达,突变型Myc基因阳性率高于野生型Myc基因,Myc基因转染骨髓造血细胞后,骨髓、肿瘤组织有较高表达,肝、肾组织则无表达.结论 外源Myc基因特异转染造血细胞可形成组织特异性转基因;突变型Myc基冈致瘤性高于野生型Myc基因.

Establishment and identification of bone morrow specific transgenk mouse model with tumorigenesis by mutant Myc retrovirus infection

Objective To establish a novel Myc gene transgenic mouse model for spontaneously forming B-lymphoma and assessing its tumorigenesis potential.Methods Freshly isolated hematopoietic pro-genitor cells served as the target for Myc gene transfer mediated by a retrovirus vector.These cells were en-grafted into C57BL/6 mice with ~(60)Co-γ ray radiation in advance.Tumor latency was measured and the tumor loaded mice were followed for survival time.Tumor was identified with histology and immunostaining.The ex-ogenous Myc gene was detected by Western blot (in liver, spleen, tumor tissue) and flow cytometry (FCM) [ in bone marrow( BM) ].Results Mice BM-infected with mutant Myc gene more readily gave rise to B-cell lymphomas than those infected with wild type Myc gene did Myc gene was expressed highly in BM and tumor tissues but not in liver and spleen.Conclusion Our model will be a tool in assessing the transforming poten-tial of Myc mutants and in studying cooperation between Myc and other oncogenes.Mutant Myc is more effec-tive than wild-type Myc in promoting B cell lymphomagenesis in mice.