Altering the expression in mice of genes by modifying their 3′ regions

Masao Kakoki, Yau Sheng Tsai, Hyung Suk Kim, Seigo Hatada, Dominic J. Ciavatta, Nobuyuki Takahashi, Larry W. Arnold, Nobuyo Maeda, Oliver Smithies

研究成果: Article査読

39 被引用数 (Scopus)

抄録

Polymorphic differences altering expression of genes without changing their products probably underlie human quantitative traits affecting risks of serious diseases, but methods for investigating such quantitative differences in animals are limited. Accordingly, we have developed a procedure for changing the expression in mice of chosen genes over a 100-fold range while retaining their chromosomal location and transcriptional controls. To develop the procedure, we first dissected the effects in embryonic stem (ES) cells of elements within and downstream of the 3′ untranslated region (UTR) of a single copy transgene at the Hprt locus. As expected, protein expression varied with the steady-state level and half-life of the mRNA. The rank order of expression with various tested 3′ regions is the same in ES cells, and in cardiomyocytes and trophoblastocytes derived from them. In mice having two functionally different native genes with modified 3′UTRs, the desired expression was obtained.

本文言語English
ページ(範囲)597-606
ページ数10
ジャーナルDevelopmental cell
6
4
DOI
出版ステータスPublished - 2004 4
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 発生生物学
  • 細胞生物学

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