FUNCTIONAL EXPRESSION AND GERMLINE TRANSMISSION OF A HUMAN-CHROMOSOMEFRAGMENT IN CHIMERIC MICE

Human chromosomes or chromosome fragments derived from normal fibrobla sts were introduced into mouse embryonic stem (ES) cells via microcell -mediated chromosome transfer (MMCT) and viable chimaeric mice were pr oduced from them. Transferred chromosomes were stably retained, and hu man genes, including immunoglobulin (Ig) kappa, heavy, lambda genes, w ere expressed in proper tissue-specific manner in adult chimaeric tiss ues. In the case of a human chromosome (hChr.) 2-derived fragment, it was found to be transmitted to the offspring through the germline. Our study demonstrates that MMCT allows for introduction of very large am ounts of foreign genetic material into mice. This novel procedure will facilitate the functional analyses of human genomes in vivo.