| 摘要 |
A non-human animal model of glucose intolerance for screening potential agents for the treatment of diseases relating from changes in glucose homeostasis, such as diabetes and other metabolic diseases such as obesity is disclosed. The present invention provides a transgenic non-human animal whose genome comprises a polynucleotide which encodes a human glycogen synthase kinase-3 (GSK-3) polypeptide, said polynucleotide being under the control of a regulatory sequence which specially directs expression of said GSK-3 polypeptide in muscle tissue. The use of a contruct comprising a specific muscle promoter regulating the expression of the human GSK-3 enzyme results in a transgenic non-human animal which develops convincing glucose intolerance, and changes in glucose homeostasis. Such as animals allow modulators of GSK-3 to be tested in vivo as possible treatments for disdeases, primarily metabolic diseases, that are characterised by changes in glucose homeostasis. |
