RGD Reference Report - Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma. - Rat Genome Database

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Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma.

Authors: Nakanishi, A  Morita, S  Iwashita, H  Sagiya, Y  Ashida, Y  Shirafuji, H  Fujisawa, Y  Nishimura, O  Fujino, M 
Citation: Nakanishi A, etal., Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5175-80. Epub 2001 Apr 10.
RGD ID: 4145661
Pubmed: PMID:11296262   (View Abstract at PubMed)
PMCID: PMC33183   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.081510898   (Journal Full-text)

Airway hyperresponsiveness (AHR), goblet cell metaplasia, and mucus overproduction are important features of bronchial asthma. To elucidate the molecular mechanisms behind these pulmonary pathologies, we examined for genes preferentially expressed in the lungs of a murine model of allergic asthma by using suppression subtractive hybridization (SSH). We identified a gene called gob-5 that had a selective expression pattern in the airway epithelium with AHR. Here, we show that gob-5, a member of the calcium-activated chloride channel family, is a key molecule in the induction of murine asthma. Intratracheal administration of adenovirus-expressing antisense gob-5 RNA into AHR-model mice efficiently suppressed the asthma phenotype, including AHR and mucus overproduction. In contrast, overexpression of gob-5 in airway epithelia by using an adenoviral vector exacerbated the asthma phenotype. Introduction of either gob-5 or hCLCA1, the human counterpart of gob-5, into the human mucoepidermoid cell line NCI-H292 induced mucus production as well as MUC5AC expression. Our results indicated that gob-5 may play a critical role in murine asthma, and its human counterpart hCLCA1 is therefore a potential target for asthma therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  ISOClca1 (Mus musculus)4145661; 4145661 RGD 
asthma  IMP 4145661 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Clca1  (chloride channel accessory 1)

Genes (Mus musculus)
Clca1  (chloride channel accessory 1)

Genes (Homo sapiens)
CLCA1  (chloride channel accessory 1)


Additional Information