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NERVOUS SYSTEM CELL BIOLOGY

Olfactory epithelia exhibit progressive functional and morphological defects in CF mice

¹Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina, Chapel Hill, North Carolina; and ²Center for Sensory Biology and Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, Maryland

Submitted 16 March 2007 ; accepted in final form 5 April 2007

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.

olfactory receptor neurons; sustentacular cells; electroolfactograms

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