Airway gene transfer in mouse nasal-airways: importance of identification of epithelial type for assessment of gene transfer

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Abstract
Mouse nasal airways are often used for the assessment of both reporter and cystic fibrosis transmembrane conductance regulator (CFTR) gene transfer to respiratory epithelia. However, the mouse nasal cavity is lined by both olfactory (OE) and respiratory epithelium (RE). Previous gene transfer studies have suggested that OE may be more efficiently transduced by adenoviral vectors than RE. However, to provide data pertinent to CFTR gene transfer in humans, measurements of CFTR function in mice by transepithelial potential difference (TPD) should be directed towards respiratory rather than olfactory epithelium. We report a new technique to mark the position of the TPD sensing cannula tip in the mouse nasal cavity that permitted us to correlate TPD measurements with epithelial cell type. Using this technique, we found TPD values did not discriminate between respiratory and olfactory epithelia. We next assessed relationships between anatomic regions accessed by the TPD cannula and epithelial type. The frequently used insertion depth of approximately 5 mm from the nose tip predominantly recorded the TPD from anterior dorsal olfactory epithelium. Measurement of the TPD of respiratory epithelium in our study was maximized by insertion of the TPD cannula probe to 2.5 mm depth. Because TPD measurements are not sensitive to epithelial type, adequate control of position and TPD catheter insertion depth are required to ensure accurate estimation of CFTR gene transfer into the target RE in the mouse nasal cavity.