ABSTRACT

Transcription control elements specific for hepatocytes are a prerequisite for targeting the expression of heterologous proteins to the liver of transgenic ani­ mals. Several promoters have been used to direct expression of transgenes to liver cells, e.g. those of the albumin, the alpha 1-antitrypsin (alAT), or the antithrom­ bin III genes (1-11). Consistent with the fact that a 1 AT (12,13) is one of the major secreted hepatic proteins, with plasma levels ranging from 1 to 3 mg/ml, the promoter of the alA T gene might be of choice for efficient, hepatospecific expression. The alAT promoter has been extensively studied, and liver-specific (14-23), macrophage-specific (24), and negative (25) cd-acting DNA sequence elements have been determined.