In vivo Expression of Adenovirus-mediated lacZ Gene in Murine Nasal Mucosa

Abstract

Adenovirus is a good tool for transferring exogenous genes into various organs because the virus has a wide spectrum of infection. In this report, we demonstrate that a recombinant adenovirus, Ax1CAlacZ, can transfer an exogenous lacZ gene into murine nasal mucosa in vivo. The efficiency of the exogenous gene expression varied for different cell types and was improved by optimizing the method of administration. In the olfactory region, the olfactory epithelia, sustentacular cells and olfactory nerve efficiently expressed lacZ gene transferred by Ax1CAlacZ using either of two administration methods, dripping or injecting. In contrast, in the respiratory region, the respiratory epithelia but not the subepithelial tissues expressed lacZ gene transferred by Ax1CAlacZ, and the efficiency of the gene transfer, which was low when the virus was administered by nasal drops, was improved when the virus was administered by injection. Our study demonstrated that gene transfer mediated by adenovirus is more efficient in the olfactory epithelia than in the respiratory epithelia, and may be applicable to nasal or paranasal diseases such as olfactory epithelial disturbances.

Ion transport across CF and normal murine olfactory and ciliated epithelium

“…In fact, in a previous study, we have reported that expression of CFTR specifically in ciliated cells of CF mice did not alter nasal PD values (26). Because some vectors more readily transduced OE compared with CE (2,17,32) it is critical to know from which cell type a "correction" is being measured. While the CF NP gives a less robust signal with regard to both Na ϩ absorption and Cl Ϫ transport defects, the nasopharyngeal PD assay may be better for ascertaining gene transfer to the ciliated epithelium of the CF mouse.…”

Survey Anatomy of the Paranasal Sinuses in the Normal Mouse

“…Ramadan and coworkers 10 have successfully used reovirus to create the first mouse model for viral sinusitis. Early gene transfer experiments using adenoviral vectors have been performed by Arimoto and colleagues 11 . This group used an adenovirus vector to transfer exogenous lacZ genes into nasal mucosa of mice.…”

“…Early gene transfer experiments using adenoviral vectors have been performed by Arimoto and colleagues. 11 This group used an adenovirus vector to transfer exogenous lacZ genes into nasal mucosa of mice. Our group and others have evaluated at the effects of nasal foreign bodies.…”

Expression of CFTR from a ciliated cell-specific promoter is ineffective at correcting nasal potential difference in CF mice

“…Although several studies have reported correction of the abnormal nasal PD in CF mice using gene transfer protocols, these studies did not attempt to target a specific cell type. [31][32][33][34] In fact, it has been reported that the olfactory epithelia is more susceptible to gene transfer by adenovirus than the respiratory epithelia, 44,45 and in one study, it was clearly demonstrated that both respiratory and olfactory epithelia were transduced. 31 To restore normal nasal bioelectrics to the CF mouse, correction of both the olfactory and the respiratory epithelia may be required.…”