Directed complementation

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 5/10 (2006.01) A01K 67/027 (2006.01) C12N 15/85 (2006.01) C12Q 1/00 (2006.01)

Patent

CA 2602594

A method of producing a tumorigenic mouse cell, the tumorigenicity of which depends on a recombinant gene of interest is disclosed. The method involves: (a) providing a conditionally tumorigenic mouse cell containing a recombinant oncogene operably linked to an inducible promoter, wherein (i) expression of the recombinant oncogene is necessary and sufficient for the tumorigenicity of the tumorigenic mouse cell, and (ii) the inducible promoter is in the uninduced state; and (b) introducing into the cell a recombinant gene of interest that functionally complements the oncogene, thereby restoring tumorigenicity without expression of the inducible recombinant oncogene. Also disclosed is a method of testing a compound for anti-tumor effects. The method includes producing tumorigenic mouse cells the tumorigenicity depends on expression of a recombinant gene of interest, implanting the cells in mice and obtaining tumors from the implanted cells, administering test compounds to the mice, and determining anti-tumor effects, if any, of the compounds.

L~invention se rapporte à un procédé de production d~une cellule de souris oncogène, dont l~oncogénicité dépend d~un gène d~intérêt recombinant. Le procédé comprend les étapes suivantes : (a) procurer une cellule de souris oncogène sous condition, contenant un oncogène recombinant lié de manière fonctionnelle à un promoteur inductible, dans lequel (i) l~expression d~un oncogène recombinant est nécessaire et suffisante pour l~oncogénicité de la cellule de souris oncogène, et (ii) le promoteur inductible est dans un état non induit ; et (b) introduire dans la cellule un gène d~intérêt recombinant qui complète de manière fonctionnelle l~oncogène, restaurant ainsi l~oncogénicité sans exprimer l~oncogène recombinant inductible. L~invention se rapporte également à un procédé de test d~un composé pour des effets anti-tumoraux. Le procédé inclut la production de cellules de souris oncogènes dont l~oncogénicité dépend de l~expression d~un gène d~intérêt recombinant, l~implantation de cellules de souris et l~obtention de tumeurs à partir de cellules implantées, l~administration de composés de test aux souris, et la détermination des effets anti-tumoraux, s~il y en a, des composés.

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