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 hybrid 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'untranslated sequences from rabbit beta-globin and SV 40 genes. Transgenic mice and rabbits that carry the htPA gene were obtained. In mice, 11 founder females were generated, and 6 of them expressed low levels (about 50 mug/ml) of htPA in their milk. Some of the transgenic mice showed rearrangements of the microinjected DNA sequences as judged by Southern blot analysis. A position-dependent expression of the transgene is suspected to occur. The only live-born founder transgenic rabbit obtained was a male, and it transmitted the transgene in a Mendelian fashion to F1 females, which expressed htPA at very low levels (8 to 50 ng/ml). Although the 1.6-kb bovine alphaS1 casein promoter that was used directs the synthesis of htPA specifically to the mammary gland, it may not be sufficient for a high level of expression.
Riego
E
E
Division of Mammalian Cell Genetics Centro de Ingeniería Genética y Biotecnología P.O. Box 6162, Havana, Cuba.
Limonta
J
J
Aguilar
A
A
Pérez
A
A
de Armas
R
R
Solano
R
R
Ramos
B
B
Castro
F O
FO
de la Fuente
J
J