The present invention provides a method of enhancing an efficiency of
homologous recombination when a gene encoding a desired protein known or
unknown in terms of function is introduced into a genome of a pluripotent
cell such as ES cell. More particularly, the present invention relates
to: a non-human animal-derived pluripotent cell comprising a foreign
enhancer at a site downstream of an immunoglobulin gene on chromosome; a
non-human animal pluripotent cell comprising a gene, which encodes a
desired protein at a site downstream of the immunoglobulin gene and
upstream of the foreign enhancer on the chromosome, said gene being in an
overexpressible state; a method of establishing said pluripotent cell;
and a chimeric non-human animal and its progeny produced by use of the
pluripotent cells and a method of producing the same. The present
invention further relates to a method of analyzing the function of a
desired protein or a gene encoding the protein by comparing a phenotype
of the chimeric non-human animal or its progeny with that of a control
animal, and/or to a method of producing a useful protein by use of the
chimeric non-human animal or its progeny.