Olfactory epithelia exhibit progressive functional and morphological defects in CF mice

Barbara R. Grubb, Troy D. Rogers, Heather M. Kulaga, Kimberlie A. Burns, Robert L. Wonsetler, Randall R. Reed, Lawrence E. Ostrowski

Research output: Contribution to journalArticlepeer-review

Abstract

In normal nasal epithelium, the olfactory receptor neurons (ORNs) are continuously replaced through the differentiation of progenitor cells. The olfactory epithelium (OE) of the cystic fibrosis (CF) mouse appears normal at birth, yet by 6 mo of age, a marked dysmorphology of sustentacular cells and a dramatic reduction in olfactory receptor neurons are evident. Electroolfactograms revealed that the odor-evoked response in 30-day-old CF mice was reduced ∼45%; in older CF mice, a ∼70% reduction was observed compared with the wild type (WT) response. Consistent with studies of CF airway epithelia, Ussing chamber studies of OE isolated from CF mice showed a lack of forskolin-stimulated Cl- secretion and an ∼12-fold increase in amiloride-sensitive sodium absorption compared with WT mice. We hypothesize that the marked hyperabsorption of Na+, most likely by olfactory sustentacular cells, leads to desiccation of the surface layer in which the sensory cilia reside, followed by degeneration of the ORNs. The CF mouse thus provides a novel model to examine the mechanisms of disease-associated loss of olfactory function.

Original languageEnglish (US)
Pages (from-to)C574-C583
JournalAmerican Journal of Physiology - Cell Physiology
Volume293
Issue number2
DOIs
StatePublished - Aug 2007

Keywords

  • Electroolfactograms
  • Olfactory receptor neurons
  • Sustentacular cells

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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