Transgenes for producing recombinant polypeptides transgenic bovine
species. A transgene for producing recombinant polypeptides in the milk
of transgenic bovine species comprises at least one expression regulation
sequence, a secretory DNA sequence encoding a secretory signal sequence
which is functional in mammary secretory cells of the bovine species and
a recombinant DNA sequence encoding the recombinant polypeptide. Also
included are methods for producing transgenic bovine species. The method
includes introducing the above transgene into an embryonal target cell of
a bovine species, transplanting the transgenic embryonic target cell
formed thereby into a recipient bovine parent and identifying at least
one female offspring which is capable of producing the recombinant
polypeptide in its milk. The invention also includes transgenic bovine
species capable of producing recombinant polypeptides in transgenic milk
as well as the milk from such transgenic bovine species and food
formulations containing one or more recombinant polypeptide. Methods are
also provided for producing transgenic non-human mammals having a
desirable phenotype. The method comprises first methylating a transgene
followed by introduction into fertilized oocytes. The oocytes are then
cultured to form pre-implantation embryos. Thereafter, at least one cell
is removed from each of the pre-implantation embryos and the DNA digested
with a restriction endonuclease capable of cleaving the methylated
transgene but incapable of cleaving the unmethylated form of the
transgene. Those pre-implantation embryos which have integrated the
transgene contain DNA which is resistant to cleavage by the restriction
endonuclease in the region containing the transgene.