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The elusive β2 subunit of sGC

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, α2i, β1 and β2, have been identified so far; however, there are only two functional enzyme forms, α11 and α21, 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.

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Correspondence to Sanchaita Sriwal Sonar.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Sonar, S.S., Eucker, T. & Schmidt, H.H. The elusive β2 subunit of sGC. BMC Pharmacol 5 (Suppl 1), P53 (2005). https://doi.org/10.1186/1471-2210-5-S1-P53

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  • DOI: https://doi.org/10.1186/1471-2210-5-S1-P53

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