Altering the expression in mice of genes by modifying their 3' regions.
Dev Cell
; 6(4): 597-606, 2004 Apr.
Article
in En
| MEDLINE
| ID: mdl-15068798
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Gene Expression Regulation
/
Mutagenesis
/
3' Untranslated Regions
/
Molecular Biology
Limits:
Animals
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2004
Document type:
Article
Affiliation country:
Estados Unidos