Endotoxin-nonresponsive model animal

A - Human Necessities – 01 – K

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A01K 67/027 (2006.01) C12N 15/09 (2006.01)

Patent

CA 2540173

It is intended to provide a nonhuman model animal which contains TIR domain, is useful in clarifying the function of TRIF-related adaptor protein (TRIF- related adaptor molecule (TRAM)) and is nonresponsive, in particular, to an endotoxin in a cell wall fraction of a gram-negative bacterium; a method of screening a promoter or an inhibitor for the response to a ligand recognized by TLR4 with the use of the endotoxin-nonresponsive nonhuman model animal as described above, and so on. An endotoxin-nonresponsive mouse, in which TRAM gene on chromosome is partly or entirely defected, the function of expressing TRAM expressed in the wild type is lost and the responsiveness to a ligand recognized by TLR4 is specifically injured, is employed in screening a promoter or an inhibitor for the response to the ligand recognized by TLR4.

L'invention concerne un animal modèle non humain contenant le domaine TIR, utile dans la clarification de la fonction d'une protéine adaptatrice TRIF (molécule adaptatrice TRIF) et ne réagissant pas, en particulier, à une endotoxine dans une fraction de paroi cellulaire d'une bactérie à germes Gram négatif. L'invention concerne également un procédé de criblage d'un promoteur ou d'un inhibiteur de la réponse à un ligand reconnu par TLR4 par utilisation de l'animal modèle non humain ne réagissant pas à une endotoxine, etc. Une souris ne réagissant pas à une endotoxine dans laquelle le gène TRAM est partiellement ou totalement défectueux sur un chromosome, la fonction d'expression de TRAM exprimé dans le type sauvage est perdue et la sensibilité à un ligand reconnu par TLR4 est spécifiquement atténuée, est utilisée dans le criblage d'un promoteur ou d'un inhibiteur de la réponse du ligand reconnu par TLR4.

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