The human ubiquitin C promoter directs high ubiquitous expression of transgenes
in mice
The human ubiquitin C promoter directs high ubiquitous expression of transgenes in mice
Marina
Schorpp
,
Richard
Jäger
1
,
Karl
Schellander
2
,
Johannes
Schenkel
1
,
Erwin F.
Wagner
2
,
Hans
Weiher
1
and
Peter
Angel*
Deutsches Krebsforschungszentrum Heidelberg, Abteilung Signaltransduktion und
Wachstumskontrolle, Im Neuenheimer Feld 280, D-69120
Heidelberg
,
Germany
,
1
Forschungszentrum Karlsruhe, Institut für Genetik, Postfach 3640, D-76021
Karlsruhe
,
Germany
and
2
Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, A-1030
Vienna
,
Austria
Received January 3, 1996;
Revised and Accepted March 19, 1996
Transgenic mice provide one of the best experimental systems to study gene
function
in vivo
. Although transgenic mice carry the additional genetic material in every cell
of the body, expression of the transgenes under the control of constitutive
promoter/enhancer units, such as the murine major histocompatibility complex
promoter H2-K
b
, the CMV enhancer/promoter, the murine
Pgk-1
promoter or the chicken cytoplasmatic [beta]
-actin
promoter is often restricted to a limited number of tissues (
1
-
5
). However, for most experimental dominant gain-of-function approaches addressing the role of a given protein in a
multicellular organism an ubiquitous expression of the transgene might be
highly desired. Here we report the application of a powerful expression vector
using the 5'-flanking region of the human ubiquitin C gene that allows very
efficient expression of a given transgene in a broad range of tissues.
The structure of the ubiquitin proteins is highly conserved during evolution. In
human, there exist several ubiquitin proteins which are encoded by a multigene
family (
6
). According to the general requirement of these proteins for ATP-dependent, non-lysosomal intracellular protein degradation ubiquitin proteins have
been found in all eukaryotic cells examined so far (for review see
7
,
8
).
Previous work has demonstrated that the human ubiquitin C promoter is very
active in conferring expression of exogenous genes following transient
transfection of the appropriate expression vectors in various cell lines (
9
; Schorpp and Angel, unpublished). In view of its powerful and ubiquitous
activity in tissue culture cells we have used the human ubiquitin C promoter as
regulatory unit to drive overexpression of two cellular genes, junB and bcl-2[alpha], in transgenic mice.
As shown in Figure
1
A, Ubi-JunB and Ubi-Bcl-2[alpha] carry 1.2 kb of the human ubiquitin C promoter region
(position -1225 to -6) fused to either the coding region of the mouse junB gene
(position +240 to +1485;
10
) or the human bcl-2[alpha] cDNA (
11
) respectively. 3' of the coding sequences, 150 bp of 3' nontranslated sequences of the human c-jun gene (
12
) and the splice and poly(A) sequences of SV40 were inserted.
REFERENCES
1 Rüther, U., Müller, W., Sumida, T., Tokuhisa, T., Rajewski, K. and Wagner, E.F. (1988) Cell 53, 847-856.MEDLINE Abstract
2 Schmidt, E.V., Christoph, G., Zeller, R. and Leder P. (1990) Mol. Cell. Biol. 10, 4406-4411.MEDLINE Abstract
3 Furth, P.A., Hennighausen, L., Baker, C., Beatty, B. and Woychick, R. (1991) Nucleic Acids Res. 19, 6205-6208.MEDLINE Abstract
4 McBurney, M.W., Staines, W,. A., Boekelheide, K., Parry, D., Jardine, K. and Pickavance, L. (1994) Dev. Dynamics 200, 278-293.
