人染色体片段在嵌合小鼠中的功能表达及种系传递

Functional expression and germline transmission of a human chromosome fragment in chimaeric mice.

作者信息

Tomizuka K, Yoshida H, Uejima H, Kugoh H, Sato K, Ohguma A, Hayasaka M, Hanaoka K, Oshimura M, Ishida I

机构信息

Central Laboratories for Key Technology, Kirin Brewery Co., LTD., Kanagawa, Japan.

出版信息

Nat Genet. 1997 Jun;16(2):133-43. doi: 10.1038/ng0697-133.

DOI:10.1038/ng0697-133

PMID:9171824

Abstract

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.

摘要

通过微细胞介导的染色体转移（MMCT）将源自正常成纤维细胞的人类染色体或染色体片段导入小鼠胚胎干细胞（ES细胞），并由此培育出了存活的嵌合小鼠。转移的染色体被稳定保留，包括免疫球蛋白（Ig）κ、重链、λ基因在内的人类基因在成年嵌合组织中以适当的组织特异性方式表达。在源自人类2号染色体（hChr.2）的片段的情况下，发现它通过种系传递给了后代。我们的研究表明，MMCT能够将大量的外源遗传物质导入小鼠体内。这一新颖的方法将有助于在体内对人类基因组进行功能分析。