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, emplying a host mouse embryo with an ablated or nonproliferating ICM.經遺傳修飾的小鼠以及用於製造該經遺傳修飾的小鼠之核酸構築體被描述。具有一編碼活化子(諸如Cre重組酶)之基因的第一小鼠被提供，該編碼活化子的基因可操作地被連結至一發育-調節的啟動子(諸如Nanog啟動子)。一具有一毒性應答者基因(諸如一編碼白喉毒素A的基因)的小鼠被提供，其中該毒性基因僅有在一活化子存在下被表現。來自於第一以及第二小鼠的交配的胚胎被提供作為宿主胚胎，其適於產生來自被引入至宿主胚胎的供體細胞的小鼠。物理上、化學上，或遺傳上剝離一小鼠胚胎的ICM，還有採用一具有被剝離或非增殖ICM的宿主小鼠胚胎來製造大體上或完全衍生自供體細胞的F0世代被描述。
