title: Gob-5 is not essential for mucus overproduction in preclinical murine models of allergic asthma.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Merck Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, PQ, H9R 4P8 Canada.
authors.forename: Annette
authors.initials: A
authors.lastname: Robichaud
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Tuck
authors.forename: Stacia
authors.initials: S
authors.lastname: Kargman
authors.forename: John
authors.initials: J
authors.lastname: Tam
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wong
authors.forename: Mark
authors.initials: M
authors.lastname: Abramovitz
authors.forename: James R
authors.initials: JR
authors.lastname: Mortimer
authors.forename: James
authors.initials: J
authors.lastname: Mortimer
authors.forename: Helen E
authors.initials: HE
authors.lastname: Burston
authors.forename: Paul
authors.initials: P
authors.lastname: Masson
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hirota
authors.forename: Deborah
authors.initials: D
authors.lastname: Slipetz
authors.forename: Brian
authors.initials: B
authors.lastname: Kennedy
authors.forename: Gary
authors.initials: G
authors.lastname: O'Neill
authors.forename: Steven
authors.initials: S
authors.lastname: Xanthoudakis
mesh_terms: D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D041981:Gastrointestinal Tract / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism; D009088:Mucoproteins / Q000235:genetics* / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering; D020545:Respiratory Mucosa / Q000166:cytology / Q000502:physiology
chemical_list: D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D009077:Mucins; D009088:Mucoproteins; D034741:RNA, Small Interfering