Deafness and stria vascularis defects in S1P2 receptor-null mice

Mari Kono, Inna A. Belyantseva, Athanasia Skoura, Gregory I. Frolenkov, Matthew F. Starost, Jennifer L. Dreier, Darcy Lidington, Steffen Sebastian Bolz, Thomas B. Friedman, Timothy Hla, Richard L. Proia

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

The S1P2 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 S1P2 receptor expression is essential for proper functioning of the auditory and vestibular systems. Auditory brainstem response analysis revealed that S1P2 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 S1P2 receptor-null mice showed markedly disturbed structures. JTE013, an S1P2 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.

Original languageEnglish
Pages (from-to)10690-10696
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number14
DOIs
StatePublished - Apr 6 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Deafness and stria vascularis defects in S1P2 receptor-null mice'. Together they form a unique fingerprint.

Cite this