Robichaud Annette, Tuck Stephanie A, Kargman Stacia, Tam John, Wong Elizabeth, Abramovitz Mark, Mortimer James R, Burston Helen E, Masson Paul, Hirota Jeremy, Slipetz Deborah, Kennedy Brian, O'Neill Gary, Xanthoudakis Steven
Department of Biochemistry and Molecular Biology, Merck Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, PQ, H9R 4P8 Canada.
Am J Respir Cell Mol Biol. 2005 Sep;33(3):303-14. doi: 10.1165/rcmb.2004-0372OC. Epub 2005 Jun 9.
Overexpression of Gob-5 has previously been linked to goblet cell metaplasia and mucin overproduction in both in vitro and in vivo model systems. In this study, Gob-5 knockout mice were generated and their phenotype was evaluated in two established preclinical models of allergic asthma. We sought to determine whether the Gob-5-null animals could produce less mucus in response to allergic challenge, and whether this would have any impact on reducing goblet cell metaplasia and airway inflammation. We found that in the absence of a proinflammatory stimulus we could not detect an overt phenotypic difference between age and sex-matched knockout and wild-type animals. Allergic challenge with ovalbumin or intranasal administration of interleukin-13 produced a robust allergic response that was similar regardless of genotype. In addition, siRNA-mediated knockdown of CLCA-1 in cultured lung epithelial cells failed to reduce mucin expression in vitro. Thus, in contrast to previously published reports, our findings show that Gob-5 expression is not essential for mucin overproduction in vitro or in murine models of allergic asthma. Furthermore, we have also exploited the use of gene expression array analysis to investigate the possibility that a compensatory mechanism, involving other genes, may act to override the requirement for Gob-5-mediated mucus overproduction.
