公开(公告)号：US07622630B2

公开(公告)日：2009-11-24

申请号：US10570116

申请日：2004-08-27

申请人： Joerg Heyer ,  Murray Robinson ,  William Rideout, III ,  Ronald Depinho ,  Steven C. Clark ,  Yinghui Zhou ,  Tyler Jacks ,  Ronan C. O'Hagan

发明人： Joerg Heyer ,  Murray Robinson ,  William Rideout, III ,  Ronald Depinho ,  Steven C. Clark ,  Yinghui Zhou ,  Tyler Jacks ,  Ronan C. O'Hagan

IPC分类号： C12N15/00 ,  A01K67/00 ,  C12N5/06

CPC分类号： A01K67/0276 ,  A01K67/0271 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/82 ,  C12N15/8509 ,  C12N2830/003

摘要： Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

摘要翻译： 公开了可用作诱导型自发癌症模型的嵌合非人哺乳动物。 通过将一个或多个经遗传修饰的胚胎干细胞（ES）细胞引入早期胚胎，然后将操作的胚胎植入替代母体中获得非人类哺乳动物。 ES细胞含有重组癌基因，并且还可能含有遗传突变，其删除或灭活肿瘤抑制基因。 不同类型癌症的模型是通过将遗传突变的不同组合引入引入早期胚胎的ES细胞来产生的。

公开(公告)号：US20090165150A1

公开(公告)日：2009-06-25

申请号：US11963358

申请日：2007-12-21

申请人： Yinghui Zhou ,  William Rideout, III ,  Joerg Heyer ,  Murray Robinson

发明人： Yinghui Zhou ,  William Rideout, III ,  Joerg Heyer ,  Murray Robinson

IPC分类号： A01K67/027 ,  C12N15/87

CPC分类号： C12N15/85 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/82 ,  C12N15/8509 ,  C12N2799/027 ,  G01N2500/10

摘要： The invention provides an improved directed complementation method for generating a conditionally tumorigenic mouse cell. In a directed complementation method, the tumorigenicity of a conditionally tumorigenic mouse cell depends on either the expression of an inducible recombinant oncogene or the expression of a recombinant gene of interest that functionally complements an uninduced recombinant oncogene. The invention provides a method of producing a tumorigenic mouse cell containing an uninduced oncogene, a recombinant gene of interest that functionally complements the uninduced oncogene, and a Cre-ER system capable of excising the recombinant gene of interest. When the Cre-ER system is activated, the recombinant gene of interest is excised. From the effect on the mouse cell it is possible to determine whether the recombinant gene of interest is a tumor maintenance gene.

摘要翻译： 本发明提供了一种用于产生有条件致瘤性小鼠细胞的改进的定向互补方法。 在定向互补方法中，条件致瘤小鼠细胞的致瘤性取决于可诱导的重组癌基因的表达或功能上补充未诱导的重组癌基因的重组感兴趣的基因的表达。 本发明提供了一种产生致瘤性小鼠细胞的方法，所述致瘤性小鼠细胞含有未诱导的癌基因，功能上补充未诱导的致癌基因的重组基因，以及能够切除感兴趣的重组基因的Cre-ER系统。 当Cre-ER系统被激活时，切除感兴趣的重组基因。 从对小鼠细胞的作用可以确定感兴趣的重组基因是否是肿瘤维持基因。