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1. 发明申请

US20090113561A1 GENE TRAP CASSETTES FOR RANDOM AND TARGETED CONDITIONAL GENE INACTIVATION 审中-公开
标题翻译：用于随机和有针对性的条件基因失活的基因捕获系统
公开(公告)号：US20090113561A1
公开(公告)日：2009-04-30
申请号：US11720231
申请日：2005-11-28
申请人： Harald Von Melchner , Frank Schnutgen , Wolfgang Wurst , Particia Ruiz , Silke De-Zolt , Thomas Floss , Jens Hansen
发明人： Harald Von Melchner , Frank Schnutgen , Wolfgang Wurst , Particia Ruiz , Silke De-Zolt , Thomas Floss , Jens Hansen
IPC分类号： A01K67/027 , C12N15/11 , C12N15/87 , C12Q1/68 , C12N5/06
CPC分类号： C12N15/1051 , C12N15/907 , C12N2799/027 , C12N2800/30 , C12N2800/60
摘要： A new type of gene trap cassette, which can induce conditional mutations, relies on directional site-specific recombination systems, which can repair and re-induce gene trap mutations when activated in succession. After the gene trap cassettes are inserted into the genome of the target organism, mutations can be activated at a particular time and place in somatic cells. The gene trap cassettes also create multipurpose alleles amendable to a wide range of post-insertional modifications. Such gene trap cassettes can be used to mutationally inactivate all cellular genes temporally and/or spatially. Cells which contain the inventive gene trap cassette can be used for identification and/or isolation of genes and for the creation of transgenic organisms to study gene function at various developmental stages, including the adult, as well as for the creation of animal models of human disease useful for in vivo drug target validation.
摘要翻译：可以诱导条件突变的新型基因陷阱盒依赖于定向位点特异性重组系统，其可以在连续激活时修复和再诱导基因陷阱突变。将基因陷阱盒插入目标生物体的基因组后，可以在特定时间激活突变并置于体细胞中。基因陷阱盒还创建了可以进行广泛的插入后修饰的多用途等位基因。这种基因捕获盒可用于在时间和/或空间上突变灭活所有细胞基因。含有本发明基因捕获盒的细胞可用于鉴定和/或分离基因，并用于产生转基因生物以研究各种发育阶段的基因功能，包括成人，以及用于创建人的动物模型用于体内药物靶标验证的疾病。

2. 发明申请

US20130024959A1 CONDITIONAL EXPRESSION OF TRANSGENES IN VIVO 审中-公开
公开(公告)号：US20130024959A1
公开(公告)日：2013-01-24
申请号：US13512235
申请日：2010-11-24
申请人： Laura Schebelle , Frank Schnütgen , Thomas Floss
发明人： Laura Schebelle , Frank Schnütgen , Thomas Floss
IPC分类号： A01K67/027 , C12N15/85
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2217/07 , A01K2217/072 , A01K2227/105 , A01K2267/0318 , C12N15/907 , C12N2800/24 , C12N2800/30
摘要： The present invention relates to a method of producing a cell comprising a conditionally active transgene in its genome, the method comprising (a) introducing into the cell a targeting vector, wherein the targeting vector comprises (i) a 5′ recombinase recognition site specifically recognised by a first recombinase, wherein the first recombinase is endogenously present in the cell or wherein the first recombinase or a nucleic acid molecule encoding said first recombinase in expressible form is introduced into the cell; followed by (ii) a 5′ recombinase recognition site specifically recognised by a second recombinase, wherein the second recombinase is not endogenously present or is not active in the cell; followed by (iii) a selection cassette comprising a positively selectable marker gene; followed by (iv) a 3′ recombinase recognition site specifically recognised by a third recombinase, wherein the third recombinase is not endogenously present or is not active in the cell; followed by (v) the transgene; followed by (vi) a 3′ recombinase recognition site specifically recognised by a fourth recombinase, wherein the fourth recombinase is endogenously present in the cell or wherein the fourth recombinase or a nucleic acid molecule encoding said fourth recombinase in expressible form is introduced into the cell; wherein the genome of the cell comprises a 5′ recombinase recognition site and a 3′ recombinase recognition site that are identical to the recombinase recognition sites of (i) and (vi), and wherein said recombinase recognition sites comprised in the genome of the cell are located 3′ of an endogenous cellular promoter such that introduction of the targeting vector into the genome by site specific recombination results in the promoter being operatively linked to the selectable marker gene; and (b) culturing the cell in the presence of a selection medium specific for the selectable marker encoded by the selectable marker gene of (iii). The present invention further relates to a method of producing a conditional transgenic non-human mammalian animal as well as to a conditional transgenic non-human mammalian animal obtainable by said method. The present invention also relates to a transgenic TDP-43 mouse, comprising a transgenic cassette in intron 1 of the mouse Tardbp gene.

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