公开(公告)号：US20090271884A1

公开(公告)日：2009-10-29

申请号：US12399109

申请日：2009-03-06

申请人： William POUEYMIROU ,  Thomas M. DECHIARA ,  Wojtek AUERBACH ,  Aris N. ECONOMIDES ,  Nicholas W. GALE ,  David FRENDEWEY ,  David M. VALENZUELA

发明人： William POUEYMIROU ,  Thomas M. DECHIARA ,  Wojtek AUERBACH ,  Aris N. ECONOMIDES ,  Nicholas W. GALE ,  David FRENDEWEY ,  David M. VALENZUELA

IPC分类号： C12N15/85 ,  C12N5/06

CPC分类号： A01K67/0271 ,  A01K67/0275 ,  A01K2207/12 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/07 ,  A01K2217/15 ,  A01K2217/203 ,  A01K2217/30 ,  A01K2227/105 ,  A01K2267/02 ,  C12N5/16 ,  C12N15/8509 ,  C12N15/907 ,  C12N2510/00 ,  C12N2517/02

摘要： Genetically modified mice and nucleic acid constructs for making the genetically modified mice are described. A first mouse having a gene encoding an activator (such as a Cre recombinase) operably linked to a developmentally-regulated promoter (such as a Nanog promoter) is provided. A second mouse having a toxic responder gene (such as a gene encoding diphtheria toxin A) is provided, where the toxic gene is expressed only in the presence of an activator, Embryos from a mating of the first and the second mouse are provided as host embryos suitable for generating mice from donor cells introduced into the host embryos. Ablating the ICM of a mouse embryo physically, chemically, or genetically is described, as well as making F0 generation mice that are substantially or in full derived from donor cells, employing a host mouse embryo with an ablated or nonproliferating ICM.

摘要翻译： 描述了用于制备遗传修饰的小鼠的转基因小鼠和核酸构建体。 提供了具有编码与发育调节的启动子（例如Nanog启动子）可操作地连接的活化剂（例如Cre重组酶）的基因的第一只小鼠。 提供具有毒性反应基因（例如编码白喉毒素A的基因）的第二只小鼠，其中毒性基因仅在活化剂存在下表达，来自第一和第二小鼠的交配的胚胎被提供为宿主 适用于从供体细胞产生小鼠的胚胎引入宿主胚胎。 描述了在物理，化学或遗传学上消除小鼠胚胎的ICM，以及使用具有消融或非增殖ICM的宿主小鼠胚胎制备基本上或完全衍生自供体细胞的F0代小鼠。