PRODUCTION OF TRANSGENIC MICE AND RABBITS THAT CARRY AND EXPRESS THE HUMAN TISSUE PLASMINOGEN-ACTIVATOR CDNA UNDER THE CONTROL OF A BOVINE ALPHA-S1 CASEIN PROMOTER

One-cell embryos from mice and rabbits were microinjected with a hybri d gene composed of 1.6 kilobases (kb) promoter/regulatory sequences of the bovine alphaS1 casein gene fused to the complementary DNA (cDNA) encoding for the human tissue plasminogen activator (htPA) and 3'untra nslated sequences from rabbit beta-globin and SV 40 genes. Transgenic mice and rabbits that carry the htPA gene were obtained. In mice, 11 f ounder females were generated, and 6 of them expressed low levels (abo ut 50 mug/ml)of htPA in their milk. Some of the transgenic mice showed rearrangements of the microinjected DNA sequences as judged by Southe rn blot analysis. A position-dependent,expression of the transgene is suspected to occur. The only live-born founder transgenic rabbit obtai ned was a male, and it transmitted the transgene in a Mendelian fashio n to F1 females, which expressed htPA at very low levels (8 to 50 ng/m l) . Although the 1.6-kb bovine alphaS1 casein promoter that was used directs the synthesis of htPA specifically to the mammary gland, it ma y not be sufficient for a high level of expression.