Investigation of S100A8 and S100A9 as potential genetic modifiers of the pulmonary phenotype in cystic fibrosis mice.

摘要

Differential global gene expression was measured in the lungs of congenic C57BL/6 (early, progressive, spontaneous inflammation) and BALB/c (undetectable inflammatory disease) Cftrtm1UNC/Cftr tm1UNC mouse models at three weeks of age (before any detectable inflammatory lesions) to gain possible insight into genetic modifiers of CF pulmonary disease. We have demonstrated that both mS100A8 and mS100A9 are overexpressed in cells of the alveolar septa and the interstitium of C57BL/6 CF lungs analyzed by microarray, semi-quantitative RT-PCR and RNA in situ hybridization. To further investigate mS100A8 as a potential modifier of CF lung disease, a C57BL/6 transgenic mouse overexpressing mS100A8 in myeloid cells under the control of the human lysozyme promoter was generated. Three independent founder lines have been identified by Southern blot analysis and the transgene was successfully transmitted to their offspring. The correct organ-specific overexpression of the mS100A8 transgene has also been confirmed by RT-PCR in a founder line.