Immune-compromised transgenic mice expressing human...

C - Chemistry – Metallurgy – 12 – Q

Patent

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C12Q 1/00 (2006.01) C12N 5/071 (2010.01) C12N 5/09 (2010.01) A01K 67/027 (2006.01) C12N 5/10 (2006.01) C12N 15/00 (2006.01) C12N 15/18 (2006.01) C12N 15/85 (2006.01) G01N 33/00 (2006.01) C07K 14/475 (2006.01)

Patent

CA 2573339

A transgenic animal model for evaluating growth, survival and/or metastasis of xenotransplanted normal or tumor cells or tissue is disclosed, in which a human growth factor, hHGF stimulates growth in vivo of human cells or tissue. A strain of Tg mice on the C3H background that is immunocompromised as a result of a homozygous scid gene has been bred which express a nucleic acid encoding hHGF/SF. The ectopically expressed hHGF/SF ligand significantly enhances growth of human tumor cell lines and explanted tumor cells or tissue that express the Met receptor for hHGF. Such animals also have an enlarged normal livers and greater than normal liver regenerative capacity. Any Met- expressing hHGF-dependent human cells, including hepatocytes and various stem cells can survive and grow in such animals.

Il est exposé un modèle d'animal transgénique servant à évaluer le développement, la survie et/ou la métastase de cellules ou de tissus normaux ou de tumeur xénotransplantés, selon lequel un facteur de croissance humain, hHGF, stimule la croissance in vivo de cellules ou de tissus humains. On élève une souche de souris Tg sur le fond de C3H qui est immunodéficiente à cause d'un gène scid homozygote, laquelle souche exprime un acide nucléique codant pour hHGF/SF. Le ligand du hHGF/SF exprimé de façon ectopique accroît considérablement le développement de lignées de cellules de tumeur humaines et de cellules ou tissus de tumeurs explantés qui expriment le récepteur Met pour le hHGF. De tels animaux ont également des foies normaux agrandis et une capacité à régénérer le foie plus grande que la normale. N'importe quelles cellules humaines dépendantes du hHGF exprimant le Met, y compris des hépatocytes et différentes cellules souche, peuvent survivre et se développer dans de tels animaux.

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