title: Deafness and stria vascularis defects in S1P2 receptor-null mice.
abstract: The S1P(2) receptor is a member of a family of G protein-coupled receptors that bind the extracellular sphingolipid metabolite sphingosine 1-phosphate with high affinity. The receptor is widely expressed and linked to multiple G protein signaling pathways, but its physiological function has remained elusive. Here we have demonstrated that S1P(2) receptor expression is essential for proper functioning of the auditory and vestibular systems. Auditory brainstem response analysis revealed that S1P(2) receptor-null mice were deaf by one month of age. These null mice exhibited multiple inner ear pathologies. However, some of the earliest cellular lesions in the cochlea were found within the stria vascularis, a barrier epithelium containing the primary vasculature of the inner ear. Between 2 and 4 weeks after birth, the basal and marginal epithelial cell barriers and the capillary bed within the stria vascularis of the S1P(2) receptor-null mice showed markedly disturbed structures. JTE013, an S1P(2) receptor-specific antagonist, blocked the S1P-induced vasoconstriction of the spiral modiolar artery, which supplies blood directly to the stria vascularis and protects its capillary bed from high perfusion pressure. Vascular disturbance within the stria vascularis is a potential mechanism that leads to deafness in the S1P(2) receptor-null mice.
authors.affiliation: Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1821, USA.
authors.forename: Mari
authors.initials: M
authors.lastname: Kono
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: Athanasia
authors.initials: A
authors.lastname: Skoura
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Frolenkov
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Starost
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dreier
authors.forename: Darcy
authors.initials: D
authors.lastname: Lidington
authors.forename: Steffen-Sebastian
authors.initials: SS
authors.lastname: Bolz
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: Timothy
authors.initials: T
authors.lastname: Hla
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
mesh_terms: D000818:Animals; D003638:Deafness / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000098:blood supply / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D049349:Receptors, Lysosphingolipid / Q000172:deficiency* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D013316:Stria Vascularis / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine