title: An exon 5-less splice variant of the extracellular calcium-sensing receptor rescues absence of the full-length receptor in the developing mouse lung.
abstract: The authors have recently demonstrated that, in the developing mouse lung, fetal plasma Ca(2+) suppresses branching morphogenesis and cell proliferation while promoting fluid secretion via activation of the extracellular Ca(2+)-sensing receptor (CaSR). The aim of the current study was to further elucidate the role of Ca(2+) in lung development by studying the effects of extracellular Ca(2+) 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.
authors.affiliation: Center for Cardiovascular Sciences, Institute for Biomedical Research, University of Birmingham, Edgbaston, United Kingdom. b.a.finney@bham.ac.uk
authors.forename: Brenda
authors.initials: B
authors.lastname: Finney
authors.forename: William J
authors.initials: WJ
authors.lastname: Wilkinson
authors.forename: Lydia
authors.initials: L
authors.lastname: Searchfield
authors.forename: Martin
authors.initials: M
authors.lastname: Cole
authors.forename: Stacey
authors.initials: S
authors.lastname: Bailey
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kemp
authors.forename: Daniela
authors.initials: D
authors.lastname: Riccardi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D005091:Exons; D005325:Fetal Organ Maturity / Q000235:genetics / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010641:Phenotype; D044169:Receptors, Calcium-Sensing / Q000235:genetics* / Q000378:metabolism*
chemical_list: D044169:Receptors, Calcium-Sensing; D002118:Calcium