Efficient human IFN-γ expression in the mammary gland of transgenic mice
Two hybrid genes (BLG-HuIFN-γ2 and BLG-HuIFN-γ3) were constructed on the basis of sheep β-lactoglobulin (BLG) and human interferon-γ(HuIFN-γ) gene sequences. They were used to direct HuIFN-γ synthesis in the mammary gland of transgenic mice. HuIFN-γ was efficiently produced in the mammary gland of transgenic mice. BLG-HuIFN-γ2 transgenic females expressed HuIFN- γ in the milk at concentrations up to 570 mg/ml, and BLG-HuIFN-γ3 transgenic females expressed up to 350 mg/ml. All females carrying the BLG- HuIFN-γ3 gene expressed HuIFN-γ in their milk. No significant changes were observed in the HuIFNγ expression level during the lactation period. Using RT-PCR analysis, ectopic expression for both hybrid genes was found in transgenic mice. Despite ectopic expression of HuIFN-γ in transgenic mice, their development and pregnancy were normal. The heritability of the HuIFN- γ expression level in milk was demonstrated up to the F2generation. This work demonstrates that hybrid genes have the potential to develop in transgenic domestic animals producing HuIFN-γ in milk.