The invention features methods of making transgenic animals, and transgenic animals made by such methods. The method includes introducing into a cell, a nucleic acid construct comprising a nucleic acid sequence encoding a heterologous polypeptide under the control of a mammary epithelial cell promoter, an insulator positioned 5' from the promoter, an insulator positioned 3' from the nucleic acid sequence encoding the polypeptide, and a prokaryotic sequence, wherein the sequence between the insulator 5' from the promoter and the insulator 3' from the nucleic acid encoding the polypeptide is substantially free of prokaryotic sequence; and allowing a transgenic mammal to develop from the cell, to thereby provide a transgenic mammal.