Gob-5 is not essential for mucus overproduction in preclinical murine models of allergic asthma.
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.
Robichaud
Annette
A
Department of Biochemistry and Molecular Biology, Merck Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, PQ, H9R 4P8 Canada.
Tuck
Stephanie A
SA
Kargman
Stacia
S
Tam
John
J
Wong
Elizabeth
E
Abramovitz
Mark
M
Mortimer
James R
JR
Mortimer
James
J
Burston
Helen E
HE
Masson
Paul
P
Hirota
Jeremy
J
Slipetz
Deborah
D
Kennedy
Brian
B
O'Neill
Gary
G
Xanthoudakis
Steven
S
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
D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D009077:Mucins; D009088:Mucoproteins; D034741:RNA, Small Interfering