Efficient human IFN-gamma expression in the mammary gland of transgenic mice

Two hybrid genes (BLG-HuIFN-gamma 2 and BLG-HuIFN-gamma 3) were constructed on the basis of sheep beta-lactoglobulin (BLG) and human interferon-gamma (HuIFN-gamma) gene sequences. They were used to direct HuIFN-gamma synthesi s in the mammary gland of transgenic mice. HuIFN-gamma was efficiently prod uced in the mammary gland of transgenic mice. BLG-HuIFN-gamma 2 transgenic females expressed HuIFN-gamma in the milli at concentrations up to 570 mg/m l, and BLG-HuIFN-gamma 3 transgenic females expressed up to 350 mg/ml. All females carrying the BLG-HuIFN-gamma 3 gene expressed HuIFN-gamma in their milk. No significant changes were observed in the HuIFN-gamma expression le vel during the lactation period, Using RT-PCR analysis, ectopic expression for both hybrid genes was found in transgenic mice. Despite ectopic express ion of HuIFN-gamma in transgenic mice, their development and pregnancy were normal. The heritability of the HuIFN-gamma expression lever in milk was d emonstrated up to the F-2 generation. This work demonstrates that hybrid ge nes have the potential to develop in transgenic domestic animals producing HuIFN-gamma in milk.