An exon 5-less splice variant of the extracellular calcium-sensing receptor rescues absence of the full-length receptor in the developing mouse lung

Finney, Brenda, Wilkinson, William James, Searchfield, Lydia ORCID: https://orcid.org/0000-0001-9640-9326, Cole, Martin, Bailey, Stacey Louise, Kemp, Paul J. ORCID: https://orcid.org/0000-0003-2773-973X and Riccardi, Daniela ORCID: https://orcid.org/0000-0002-7322-3163 2011. An exon 5-less splice variant of the extracellular calcium-sensing receptor rescues absence of the full-length receptor in the developing mouse lung. Experimental Lung Research 37 (5) , pp. 269-278. 10.3109/01902148.2010.545471

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Abstract

The authors have recently demonstrated that, in the developing mouse lung, fetal plasma Ca2+ suppresses branching morphogenesis and cell proliferation while promoting fluid secretion via activation of the extracellular Ca2+-sensing receptor (CaSR). The aim of the current study was to further elucidate the role of Ca2+ in lung development by studying the effects of extracellular Ca2+ on fetal lung development in mice lacking the CaSR. These mice were produced by exon 5 deletion in the CaSR gene. Since such a maneuver has been known to induce the expression of an exon 5-less splice variant of the CaSR in some tissues, the molecular and functional expression of this splice variant in the developing mouse lung was also investigated. Whereas there was a mild in vivo phenotype observed in these mice, in vitro sensitivity of Casr−/− lung explants to specific activators of the CaSR was unaffected. These results imply that compensatory expression of an exon 5-less splice variant rescues CaSR function in this mouse model and therefore a lung-specific, complete CaSR knockout model must be developed to fully appreciate the role for this receptor in lung development and the contribution of its ablation to postnatal respiratory disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Uncontrolled Keywords:	branching morphogenesis; exon 5-less splice variant; extracellular calcium-sensing receptor; lung development
Publisher:	Informa Healthcare
ISSN:	0190-2148
Last Modified:	29 Aug 2024 01:09
URI:	https://orca.cardiff.ac.uk/id/eprint/24687

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