Developmental regulation and tissue-specific expression of a chimaeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic animals.

Expression of the bovine growth hormone (bGH) gene, directed by the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter, in transgenic animals was investigated. Different lengths of the 5' PEPCK promoter-regulatory domain were utilized to control bGH expression; these included -2000/+73, -460/+73, -355/+73, and -174/+73. The chimaeric PEPCK/bGH gene containing -460/+73 of PEPCK 5' flanking sequence (PEPCK/bGH(460] is regulated by cAMP, insulin, and dexamethasone in the same manner as the endogenous PEPCK gene. This PEPCK promoter-regulatory domain also controls the tissue-specific expression of the bGH gene to liver, kidney, adipose tissue, jejunum and mammary gland. Furthermore, the correct developmental pattern of expression is observed in the mouse lines which contain PEPCK/bGH(460). The transgene mRNA is not detected during fetal development until Day 19. At Day 1 after birth, due to alterations in the insulin:glucagon ratio, the amounts of transgene mRNA are greatly increased, similar to the endogenous PEPCK gene.