HETEROLOGOUS PROTEIN EXPRESSION BY TRANSIMMORTALIZED DIFFERENTIATED LIVER-CELL LINES DERIVED FROM TRANSGENIC MICE (HEPATOMAS-ALPHA-1 ANTITRYPSIN ONC MOUSE)

A number of therapeutic plasma proteins are synthesized by human hepatocytes. Since many of these proteins undergo liver-specific post-translational modifications which are required for full biological activity, it may therefore be necessary to develop hepatocyte-based expression systems for their production. Using transgenic mice we have developed a transimmortalisation technique for the isolation of differentiated hepatic cell lines, already engineered to secrete human α1 antitrypsin (α1 AT), a plasma protein which is produced mainly in liver cells. This was achieved by co-expression of the mouse c-myc proto-oncogene and a genomic copy of the human α1 AT gene, both under the control of the human α1 AT promoter. Transgenic mice carrying this construct developed hepatomas producing human α1 AT. Under defined culture conditions, cell lines secreting active α1 AT were derived from these tumours. These cells maintain a differentiated hepatic phenotype and continue to secrete human α1 AT for at least 40 generations. © 1990.