• Poster presentation
• Open Access

• Published: 16 June 2005

NO's major physiological receptor is the soluble guanylyl cyclase (sGC). sGC exist as heterodimers of 2 subunits, α/β. Heterodimerization between both the α and β subunit is essential for sGC's enzymatic activity. Five subunits, termed α₁, α₂, α_2i, β₁ and β₂, have been identified so far; however, there are only two functional enzyme forms, α₁/β₁ and α₂/β₁, that appear to form in vivo at the protein level. The β₂ sGC subunit is the most obscure isoform of all the subunits and its physiological relevance is until now unresolved. Here we clearly show a ubiquitous expression of sGCβ₂ in wildtype mice. Cloning of this subunit revealed a 45 base pairs shorter splice variant in the 7th exon along with the predicted sGCβ₂ mRNA. This shorter variant is expressed along with the sGCβ₂ in all major organs. To further characterize the role of this subunit, we have generated a sGCβ₂ knockout mice and back-crossed by speed-congenics. The heme NO binding domain (HNOB), comprising exons 5, 6 and 7 were deleted. Analysis of the knockout mice revealed no transcripts of sGCβ₂ in all the major organs suggesting the sGCβ₂ knockout mice are complete knockouts. These animals have been backcrossed by marker assisted backcrossing (speed congenics), with over 98 percent of the C57/BL6J (recipient) background incorporated. The phenotypic analysis of these knockout mice will help unravel the role of this subunit in the NO/cGMP cascade.