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BMC Pharmacology

Open AccessOral presentationAnalysis of mice with genetic modifications of PKG IFranz Hofmann*1, Robert Lukowski1, Dominik Bernhard1, Pascal Weinmeister1, Silke Weber1, Susanne Feil2, Jens Schlossmann1, Jörg W Wegener1 and Robert Feil2

Address: 1Institut für Pharmakologie und Toxikologie, TU München, Germany and 2Interfakultäres Institut für Biochemie, Universität Tübingen, Germany

Email: Franz Hofmann* - Hofmann@ipt.med.tu-muenchen.de

* Corresponding author

The signaling molecule nitric oxide (NO) exerts both ben-eficial and deleterious effects on the vasculature; however,the molecular signaling pathways are incompletely under-stood. In smooth muscle cells (SMCs), the second mes-senger cyclic guanosine monophosphate (cGMP)mediates many effects of NO via the activation of cGMP-dependent protein kinase type I (cGKI). The cGKI gene,prkg1, encodes two isoforms, cGKIα and cGKIβ, both ofwhich are expressed in SMCs. The isoforms differ only intheir individual amino-terminal ends, which mediate theinteraction with partner proteins and target the kinases todifferent subcellular compartments. Conventional knock-outs carrying a cGKI null mutation (cGKI-/-) show multi-ple phenotypes. These animals are difficult to analyse,since most die before adulthood. Recently, two mouselines were generated that express either the cGKIα orcGKIβ isoform exclusively in SMCs of cGKI-/- mice. Thesemouse lines allow an isoform specific of individualsmooth muscle functions in adult "healthy" animals. 8-Br-cGMP treatment of aortic SMCs from rescued micereduced norepinephrine- and depolarization-inducedCa2+-increases to wild type levels. In addition, the 8-Br-cGMP-induced relaxation of hormone contracted aortaand jejunum was intact in the rescued animals. Finally,telemetric blood pressure recordings in awake, freely mov-ing mice revealed no differences between rescued andcontrol (wild type) mice. Taken together, these results sug-gest that both isoforms can rescue a major part of the

cGMP/cGKI signaling in SMCs and either isoform cancompensate for the other in the modulation of vasculartone. Irrespective of the reconstituting isozyme, 50% ofthe rescued cGKIα and cGKIβ mice die within 52 weeks.Abnormalities found in the mouse lines that possiblycause premature death will be discussed.

from 3rd International Conference on cGMP Generators, Effectors and Therapeutic ImplicationsDresden, Germany. 15–17 June 2007

Published: 25 July 2007

BMC Pharmacology 2007, 7(Suppl 1):S15 doi:10.1186/1471-2210-7-S1-S15

<supplement> <title> <p>3^rdInternational Conference on cGMP Generators, Effectors and Therapeutic Implications</p> </title> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1471-2210-7-S1-full.pdf">here</a>.</note> </supplement>

This abstract is available from: http://www.biomedcentral.com/1471-2210/7/S1/S15

© 2007 Hofmann et al; licensee BioMed Central Ltd.