FIG. 10.

AdV-mediated gene transfer to murine tracheal epithelium is enhanced by GPI-hCAR only in the absence of Muc1 glycoprotein from the lumenal surface. (A) Representative photomicrographs of excised murine tracheas displaying LacZ expression in the surface epithelium. Tracheal epithelia from control (i), GPI-hCAR transgenic (ii), Muc1^−/− knockout (iii), and GPI-hCAR/Muc1^−/− (iv) animals were inoculated with AdVLacZ (20 μl at 10¹¹ particles/ml) and assessed 48 h later for gene transfer. Histological sections of murine tracheal epithelia from GPI-hCAR/Muc1^−/− animals revealed that airway surface epithelial cells expressed the transgene, with both ciliated cells (v, arrows) and Clara cells (vi, arrows) being transduced by AdVLacZ. (B) Quantitative morphological analyses of the percentages of epithelial surface area exposed to AdVLacZ that expressed LacZ after 48 h for tracheas derived from Muc1^+/+ (n = 30), GPI-hCAR/Muc1^+/+ (n = 30), Muc1^−/− (n = 7), and GPI-hCAR/Muc1^−/− (n = 22) animals. For comparison, the percentage of epithelial surface area expressing LacZ after sodium caprate treatment (25 mM) prior to AdVLacZ inoculation is shown (n = 12). Data represent means ± SE. * and **, statistically significant differences, with P < 0.0002 and P < 0.02, respectively.