An efficient system for genetic modification and large-scale cloning o
f cattle is of importance for agriculture, biotechnology, and human me
dicine. Here, actively dividing fetal fibroblasts were genetically mod
ified with a marker gene, a clonal line was selected, and the cells we
re fused to enucleated mature oocytes. Out of 28 embryos transferred t
o 11 recipient cows, three healthy, identical, transgenic calves were
generated. Furthermore, the life-span of near senescent fibroblasts co
uld be extended by nuclear transfer, as indicated by population doubli
ngs in fibroblast lines derived from a 40-day-old fetal clone. With th
e ability to extend the life-span of these primary cultured cells, thi
s system would be useful for inducing complex genetic modifications in
cattle.