SPECIFIC COMBINATIONS OF HUMAN SERUM-ALBUMIN INTRONS DIRECT HIGH-LEVEL EXPRESSION OF ALBUMIN IN TRANSFECTED COS CELLS AND IN THE MILK OF TRANSGENIC MICE

A new series of expression vectors, each comprised of the beta-lactogl obulin (BLG) promoter driving one of a variety of human serum albumin (HSA) minigenes or the entire gene, were evaluated for their ability t o direct expression of HSA in vitro in COS tissue culture cells and in to the milk of transgenic mice. Vectors directed a hierarchy of expres sion levels in vitro dependent upon the specific complement of HSA int rons included. HSA introns acted in a synergistic manner. In addition, minigenes comprised of specific subsets of introns were more efficaci ous than the entire HSA gene with all of its introns. Transgenic mice expressed as much as 10 mg ml(-1) of HSA in their milk. Vectors compri sed of specific intron subsets directed levels at 1 mg ml(-1) or great er in the milk of 20% of generated transgenics. A statistical correlat ion between the expression level trend in vitro with the trend of expr ession in vivo (% which express) at detectable levels (p = 0.0015) and at the level of greater than 0.1 mg ml(-1) (p = 0.0156) was demonstra ted. A weak correlation existed (p = 0.0526) at in vivo levels of 1 mg ml(-1) or greater. These new vectors are expected to direct the produ ction of high levels of HSA in the milk of a large percentage of gener ated transgenic dairy animals.