Cloning of human genomic lactoferrin sequence and expression in the mammary glands of transgenic animals.

Abstract

Transgenic animals which express foreign proteins in their mammary glands have been useful tools for the mass production of human proteins1. DNA sequences conferring mammary-specific expression to the foreign genes of interest have been derived from the promoters of major milk protein genes such as whey acidic protein2,3, β-lactoglobulin4, α-casein5, β-casein6,7 and α-lactalbumin8. In most studies, the foreign proteins were synthesized and secreted into the milk although in some cases the expression of the transgene was not restricted to the mammary gland. The advent of such technology has prompted researches of using transgenic animals as bioreactors. Pharmaceuticals and other useful human proteins such as human (αl-antitrypsin4,9, tissue plasminogen activator2,10, human serum albumin11, and human hemoglobin12 were produced in transgenic mouse, rat, sheep, goat, and pig. Although very few transgenic systems have been described where the expression level of the transgene approached that of the endogenous gene, many of them proved to be successful by expressing more than a gram of transgene product per liter of milk.