IκB kinase-α (IKKα) is required in lymphoid organogesis and mammary gland development. It has been reported that expression of IKKα is up-regulated in human cancers. IKKα-knockdown mouse model was established in order to study of its physiological function and its role in tumorigenesis. IKKα-knockdown lentiviral vectors were injected into the subzonal space between the cytoplasmic membrane and the zona pellucida. Transgenic mice were generated with the average positive rate of 15% and the IKKα gene knockdown in this mouse model was characterized. IKKα mRNA levels were markedly lower in blood samples collected from transgenic mice as compared to wild type mice. This IKKα-knockdown transgenic mouse model proves to be a useful tool to study physiological function of IKKα gene in vivo. Further phenotype analysis is under the way.