Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme
Weber S, Bernhard D, Lukowski R, Weinmeister P, Wörner R, Wegener J, Valtcheva N, Feil S, Schlossmann J, Hofmann F, Feil R (2007)
Circulation Research 101(11): 1096-1103.
Zeitschriftenaufsatz
| Veröffentlicht | Englisch
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Autor*in
Weber, Silke;
Bernhard, Dominik;
Lukowski, Robert;
Weinmeister, Pascal;
Wörner, René;
Wegener, JörgUniBi ;
Valtcheva, Nadejda;
Feil, Susanne;
Schlossmann, Jens;
Hofmann, Franz;
Feil, Robert
Abstract / Bemerkung
Smooth muscle expresses the Iα and the Iβ isoforms of cGMP-dependent protein kinase I (cGKI). Inactivation of the murine cGKI geneprkg1leads to multiple phenotypes and premature death at ≈6 weeks. We reconstituted mice with the cGKIα or -Iβ isozyme to test which isozyme was needed to support basic smooth muscle functions. Mice were generated by gene targeting. The cGKIα or the -Iβ coding sequences were placed under the control of the SM22α promoter to express either isoform selectively in smooth muscle cells (SM-Iα or SM-Iβ transgene). To generate smooth muscle–specific cGKIα or cGKIβ rescue mice, the SM-Iα or SM-Iβ transgenes were crossed on a cGKI−/−genetic background. The levels of cGKIα or -Iβ expression were comparable to endogenous cGKI expression in wild-type aortic and intestinal smooth muscles. In cGKIα or -Iβ rescue mice, expression of the isozymes was not detectable in non–smooth muscle tissues and cells. Median survival time of the Iα and Iβ rescue mice was 52 weeks. Both isozymes mediated the 8-bromo-cGMP–induced relaxation of precontracted jejunum and aorta muscle strips. Activation of both isozymes reduced hormone- or K+-induced [Ca2+]ilevels. The cGKIα and cGKIβ rescue mice did not show a significant difference in intestinal passage time of BaSO4in comparison with wild-type animals. Telemetric blood pressure measurements in conscious freely moving animals did not show differences between rescues and control mice in basal blood pressure and its regulation by DETA-NO, sodium nitroprusside, carbachol, or Y-27632. These results show that cGKI in smooth muscle is essential and that either cGKI isozyme alone can rescue basic vascular and intestinal smooth muscle functions.
Erscheinungsjahr
2007
Zeitschriftentitel
Circulation Research
Band
101
Ausgabe
11
Seite(n)
1096-1103
ISSN
0009-7330
eISSN
1524-4571
Page URI
https://pub.uni-bielefeld.de/record/2984491
Zitieren
Weber S, Bernhard D, Lukowski R, et al. Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme. Circulation Research. 2007;101(11):1096-1103.
Weber, S., Bernhard, D., Lukowski, R., Weinmeister, P., Wörner, R., Wegener, J., Valtcheva, N., et al. (2007). Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme. Circulation Research, 101(11), 1096-1103. https://doi.org/10.1161/CIRCRESAHA.107.154351
Weber, Silke, Bernhard, Dominik, Lukowski, Robert, Weinmeister, Pascal, Wörner, René, Wegener, Jörg, Valtcheva, Nadejda, et al. 2007. “Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme”. Circulation Research 101 (11): 1096-1103.
Weber, S., Bernhard, D., Lukowski, R., Weinmeister, P., Wörner, R., Wegener, J., Valtcheva, N., Feil, S., Schlossmann, J., Hofmann, F., et al. (2007). Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme. Circulation Research 101, 1096-1103.
Weber, S., et al., 2007. Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme. Circulation Research, 101(11), p 1096-1103.
S. Weber, et al., “Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme”, Circulation Research, vol. 101, 2007, pp. 1096-1103.
Weber, S., Bernhard, D., Lukowski, R., Weinmeister, P., Wörner, R., Wegener, J., Valtcheva, N., Feil, S., Schlossmann, J., Hofmann, F., Feil, R.: Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme. Circulation Research. 101, 1096-1103 (2007).
Weber, Silke, Bernhard, Dominik, Lukowski, Robert, Weinmeister, Pascal, Wörner, René, Wegener, Jörg, Valtcheva, Nadejda, Feil, Susanne, Schlossmann, Jens, Hofmann, Franz, and Feil, Robert. “Rescue of cGMP Kinase I Knockout Mice by Smooth Muscle–Specific Expression of Either Isozyme”. Circulation Research 101.11 (2007): 1096-1103.