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

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 ol factory (OE) and respiratory epithelium (RE). Previous gene transfer studie s have suggested that OE may be more efficiently transduced by adenoviral v ectors 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 olfact ory epithelium. We report a new technique to mark the position of the TPD s ensing 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 epitheli a. We next assessed relationships between anatomic regions accessed by the TPD cannula and epithelial type. The frequently used insertion depth of app roximately 5 mm from the nose tip predominantly recorded the TPD from anter ior dorsal olfactory epithelium. Measurement of the TPD of respiratory epit helium 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 require d to ensure accurate estimation of CFTR gene transfer into the target RE in the mouse nasal cavity.