title: Altering the expression in mice of genes by modifying their 3' regions.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Masao
authors.initials: M
authors.lastname: Kakoki
authors.forename: Yau-Sheng
authors.initials: YS
authors.lastname: Tsai
authors.forename: Hyung-Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Seigo
authors.initials: S
authors.lastname: Hatada
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Ciavatta
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Larry W
authors.initials: LW
authors.lastname: Arnold
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.forename: Oliver
authors.initials: O
authors.lastname: Smithies
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D008967:Molecular Biology / Q000379:methods*; D016296:Mutagenesis / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins