Conditional inactivation of the NO-sensitive guanylyl cyclase isoforms (α1β1, α2β1) in mice
© BioMed Central Ltd 2005
Published: 16 June 2005
Signalling via NO/cGMP regulates diverse physiological processes such as smooth muscle relaxation, inhibition of platelet aggregation and modulation of neurotransmission. To elevate intracellular cGMP concentrations the signal molecule nitric oxide (NO) binds to the prosthetic heme group of the NO-sensitive guanylyl cyclase (GC), a heterodimeric enzyme composed of one α and one β subunit.
Two different isoforms of the NO-sensitive GC have been shown to exist in vivo; the α1β1 and the α2β1 heterodimer revealing undistinguishable enzymatic properties. Investigation of the tissue distribution of both GC isoforms revealed a major occurrence of the α2β1 isoform in brain, whereas in all other tissues tested, the α1β1 heterodimer was the predominating isoform.
In order to study the NO/cGMP signalling and to analyse the functional significance of the GC isoforms, we have generated conditional knockout mice, in which the gene coding for the α1- or the α2-subunit can be deleted using the Cre/loxP system.
Here we report on the phenotypes of mice with deficiency of the α1- or the α2-subunit of the NO-sensitive GC in all tissues.