Loading patent…
AssigneeMacau University of Science and Technology
InventorsLiang Liu, Ting Li, Kam Wai Wong, Zhihong Jiang, Hua Zhou
Estimating the term…
The present invention provides an in vivo platform for identifying and determining therapeutic or prophylactic activity of test compounds in delay-type hypersensitivity (DTH) and other inflammatory or cancerous diseases mediated by activation of IKK-βC46A mutants. The in vivo platform of the present invention is a non-human transgenic mammal, e.g., a mouse model, with a site directed mutagenesis at a cysteine residue replaced by alanine in IKK-β protein kinase. The site directed mutagenesis is introduced by a specially designed targeting vector containing a transversion in exon 3 of the Ikbkb genes encoding the IKK-β. The present invention also provides methods for generating the transgenic mammal and for determining and identifying compounds that can inhibit activation of IKK-βC46A mutants.
A homozygous IKK-βC46A transgenic, knock-in, C57BL/6J mouse whose genome comprises a transgene encoding a single cysteine-to-alanine mutation at position 46 (C46A) in the endogenous amino acid sequence of SEQ ID NO:2, wherein the transgenic mouse comprises kidney tissues with a stronger in vivo kinase activity of IKK-β and ear tissues with an enhanced in vivo inflammatory response to a delay-type hypersensitivity (DTH)-inducing agent relative to an equal amount of the respective tissues from a C57BL/6J wild-type mouse.
Dependencies are inferred from the claim text.