Functional expression and germline transmission of a human chromosome fragment in chimaeric mice.
Human chromosomes or chromosome fragments derived from normal fibroblasts were introduced into mouse embryonic stem (ES) cells via microcell-mediated chromosome transfer (MMCT) and viable chimaeric mice were produced from them. Transferred chromosomes were stably retained, and human genes, including immunoglobulin (Ig) kappa, heavy, lambda genes, were expressed in proper tissue-specific manner in adult chimaeric tissues. 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 amounts of foreign genetic material into mice. This novel procedure will facilitate the functional analyses of human genomes in vivo.
Tomizuka
K
K
Central Laboratories for Key Technology, Kirin Brewery Co., LTD., Kanagawa, Japan.
Yoshida
H
H
Uejima
H
H
Kugoh
H
H
Sato
K
K
Ohguma
A
A
Hayasaka
M
M
Hanaoka
K
K
Oshimura
M
M
Ishida
I
I
D000818:Animals; D002459:Cell Fusion; D002678:Chimera; D002877:Chromosomes, Human; D005260:Female; D018014:Gene Transfer Techniques; D015894:Genome, Human; D018095:Germ-Line Mutation; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D013234:Stem Cells
D007136:Immunoglobulins; D012333:RNA, Messenger