High level expression of the bioactive human interleukin-10 in milk of transgenic mice

Abstract

Human interleukin-10 (hIL-10) has wide spectrum of anti-inflammatory activities and has shown a potential to be used for treatment of inflammatory or immune illness. In this study, transgenic mice that over-express human interleukin-10 (IL-10) in their milk were generated using a bovine β-casein/human IL-10 hybrid gene. After cloning of the IL-10 gene, a 22 kb hybrid gene was constructed by linking a 10 kb promoter sequence of the bovine β-casein gene to the cloned 12 kb IL-10 gene. In six of the eight transgenic mice, the transgene RNA was expressed only in the mammary gland and in the other two mice, it was also slightly expressed in the lung. The highest human IL-10 level in milk was 1620 μg ml-1. Notably, transgenes in all the eight transgenic mice were expressed regardless of the integration site even though no correlation was shown between the copy numbers of the transgene and expression level. These results suggest that the genomic sequence of the human IL-10 gene can induce the IL-10 expression at high levels under the control of the bovine β-casein promoter. © 2003 Elsevier Science B.V. All rights reserved.