The present invention is transgenic chickens obtained from long-term cultures of avian PGCs and techniques to produce and transgenic birds derived from prolonged PGC cultures. In some embodiments, these PGCs can be transfected with genetic constructs to modify the
DNA of the PGC, specifically to introduce a
transgene encoding an
exogenous protein. When combined with a host
avian embryo by known procedures, those modified PGCs are transmitted through the
germline to yield transgenic
offspring. This invention includes compositions comprising long-term cultures of PGCs and
offspring derived from them that are genetically modified. The genetic modifications introduced into PGCs to achieve the
gene inactivation may also include, but are not restricted to, random integrations of transgenes into the
genome, transgenes inserted into the
promoter region of genes, transgenes inserted into repetitive elements in the
genome, site specific changes to the
genome that are introduced using
integrase, site specific changes to the genome introduced by
homologous recombination, and conditional mutations introduced into the genome by excising
DNA that is flanked by lox sites or other sequences that are substrates for
site specific recombination.