Heme-regulated eukaryotic initiation factor 2 alpha kinase...

C - Chemistry – Metallurgy – 12 – Q

Patent

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C12Q 1/48 (2006.01) A01K 67/027 (2006.01) A61K 31/7088 (2006.01) A61K 38/45 (2006.01) A61K 48/00 (2006.01) A61P 7/06 (2006.01) C12N 15/85 (2006.01) C12Q 1/00 (2006.01) C12Q 1/02 (2006.01) G01N 33/573 (2006.01)

Patent

CA 2469679

The targeted disruption of the gene encoding the heme-regulated eIF2-kinase (HRI) in mice establishes that HRI, which is expressed predominantly in erythroid cells, regulates the synthesis of both alpha and beta globins in red blood cell precursors by inhibiting the general translation initiation factor eIF2. HRI is a physiological regulator of gene expression in the erythroid lineage and acts both as a sensor of heme and an effector controlling the initiation of translation. Accordingly regulation of HRI can be used to control proliferation of cells, especially cells of hematopoietic origin, using compositions and compounds identified using HRI deficient mice.

L'invention concerne la disruption ciblée du gène codant la kinase-eIF2 (HRI) régulée par l'hème chez la souris. Selon cette disruption, il est établit que la HRI, qui est essentiellement exprimée dans les cellules érythrocytes, régule la synthèse des globines alpha et béta dans les précurseurs des globules rouges en inhibant le facteur d'initiation de la translation générale eIF2. HRI est un régulateur physiologique de l'expression génique dans la lignée des érythrocytes et sert de capteur de l'hème et d'effecteur contrôlant l'initiation de la translation. Par conséquent, la régulation de la HRI peut permettre de contrôler la prolifération cellulaire, particulièrement, des cellules d'origine hématopoïétique, à l'aide de compositions et de composés identifés à l'aide de souris présentant une carence en HRI.

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