Knock-in mice expressing cGKIα or cGKIβ selectively in smooth muscle

Many effects of NO and natriuretic peptides in smooth muscle cells (SMCs) are mediated by activation of cGMP synthesis and the cGMP-dependent protein kinase type I (cGKI). However, the molecular mechanisms of cGKI action, particularly the specific roles of the two cGKI isoforms, cGKIα and cGKIβ, are not clear. To analyze the functions of cGKI isoforms in SMCs, transgenic mice which express the cGKIα or cGKIβ isoform selectively in SMCs were generated (SM-cGKIα or SM-cGKIβ mice. The cGKIα or cGKIβ encoding sequences were integrated into the SMC-specific SM22α gene by homologous recombination in ES cells. Chimeric mice were generated by injection of correctly targeted ES cells into mouse blastocysts. After germline transmission of the modified alleles, the SM-cGKIα and SM-cGKIβ "knock-in" mouse lines could be established. These mouse lines are currently bred on a cGKI-deficient background to eliminate endogenous cGKI expression. This deletion/rescue strategy should help to clarify the specific functions of cGKIα and cGKIβ in SMCs.