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 approximately 45%; in older CF mice, a approximately 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 approximately 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetophenones / pharmacology
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Adenylyl Cyclases / metabolism
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Aging / pathology
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Aldehydes / pharmacology
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Amiloride / pharmacology
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Animals
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Chlorides / metabolism
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Colforsin / pharmacology
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Cyclic AMP / metabolism
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Cystic Fibrosis / genetics
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Cystic Fibrosis / metabolism*
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Cystic Fibrosis / pathology
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Cystic Fibrosis / physiopathology
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Cystic Fibrosis Transmembrane Conductance Regulator / deficiency
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Cystic Fibrosis Transmembrane Conductance Regulator / genetics
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Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Enzyme Activators / pharmacology
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Mice
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Mice, Inbred CFTR
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Microscopy, Electron, Scanning
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Odorants
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Olfactory Mucosa / drug effects
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Olfactory Mucosa / metabolism*
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Olfactory Mucosa / physiopathology
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Olfactory Mucosa / ultrastructure
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Olfactory Receptor Neurons / drug effects
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Olfactory Receptor Neurons / metabolism*
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Olfactory Receptor Neurons / physiopathology
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Olfactory Receptor Neurons / ultrastructure
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Pentanols / pharmacology
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RNA, Messenger / metabolism
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Receptors, Odorant / drug effects
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Receptors, Odorant / metabolism*
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Smell* / drug effects
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Sodium / metabolism
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Sodium Channel Blockers / pharmacology
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Time Factors
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Tissue Culture Techniques
Substances
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Acetophenones
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Aldehydes
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Chlorides
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Enzyme Activators
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Pentanols
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RNA, Messenger
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Receptors, Odorant
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Sodium Channel Blockers
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Cystic Fibrosis Transmembrane Conductance Regulator
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Colforsin
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Amiloride
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amyl acetate
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Sodium
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Cyclic AMP
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Adenylyl Cyclases
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acetophenone