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

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)597-606
Number of pages10
JournalDevelopmental Cell
Volume6
Issue number4
DOIs
Publication statusPublished - 2004 Apr 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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