Recombinant Factor IX characterized by a high percentage of active protein
can be obtained in the milk of transgenic animals that incorporate
chimeric DNA molecules according to the present invention. Transgenic
animals of the present invention are produced by introducing into
developing embryos DNA that encodes Factor IX, such that the foreign DNA
is stably incorporated in the DNA of germ line cells of the mature
animal. Particularly efficient expression was accomplished using a
chimeric construct comprising a mammary gland specific promoter, Factor
IX cDNA that lacked the complete or any portion of the 5'-untranslated
and 3'-untranslated region, which is substituted with a 5-' and 3'-end of
the mouse whey acidic protein gene. In vitro cell cultures of cells
explanted from the transgenic mammal of the invention and methods of
producing Factor IX from such said culture and methods of treating
hemophilia B are also described.