RGD Reference Report - Elevation of susceptibility to ozone-induced acute tracheobronchial injury in transgenic mice deficient in Clara cell secretory protein. - Rat Genome Database

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Elevation of susceptibility to ozone-induced acute tracheobronchial injury in transgenic mice deficient in Clara cell secretory protein.

Authors: Plopper, CG  Mango, GW  Hatch, GE  Wong, VJ  Toskala, E  Reynolds, SD  Tarkington, BK  Stripp, BR 
Citation: Plopper CG, etal., Toxicol Appl Pharmacol. 2006 May 15;213(1):74-85. Epub 2005 Oct 14.
RGD ID: 5144142
Pubmed: PMID:16226776   (View Abstract at PubMed)
DOI: DOI:10.1016/j.taap.2005.09.003   (Journal Full-text)

Increases in Clara cell abundance or cellular expression of Clara cell secretory protein (CCSP) may cause increased tolerance of the lung to acute oxidant injury by repeated exposure to ozone (O3). This study defines how disruption of the gene for CCSP synthesis affects the susceptibility of tracheobronchial epithelium to acute oxidant injury. Mice homozygous for a null allele of the CCSP gene (CCSP-/-) and wild type (CCSP+/+) littermates were exposed to ozone (0.2 ppm, 8 h; 1 ppm, 8 h) or filtered air. Injury was evaluated by light and scanning electron microscopy, and the abundance of necrotic, ciliated, and nonciliated cells was estimated by morphometry. Proximal and midlevel intrapulmonary airways and terminal bronchioles were evaluated. There was no difference in airway epithelial composition between CCSP+/+ and CCSP-/- mice exposed to filtered air, and exposure to 0.2 ppm ozone caused little injury to the epithelium of both CCSP+/+ and CCSP-/- mice. After exposure to 1.0 ppm ozone, CCSP-/- mice suffered from a greater degree of epithelial injury throughout the airways compared to CCSP+/+ mice. CCSP-/- mice had both ciliated and nonciliated cell injury. Furthermore, lack of CCSP was associated with a shift in airway injury to include proximal airway generations. Therefore, we conclude that CCSP modulates the susceptibility of the epithelium to oxidant-induced injury. Whether this is due to the presence of CCSP on the acellular lining layer surface and/or its intracellular distribution in the secretory cell population needs to be defined.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Acute Lung Injury  ISOScgb1a1 (Mus musculus)5144142; 5144142 RGD 
Acute Lung Injury  IMP 5144142 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Scgb1a1  (secretoglobin family 1A member 1)

Genes (Mus musculus)
Scgb1a1  (secretoglobin, family 1A, member 1)

Genes (Homo sapiens)
SCGB1A1  (secretoglobin family 1A member 1)


Additional Information