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Background  Secretoglobin 1A1 (SCGB 1A1), also called Clara cell secretory protein, is the most abundantly secreted protein of the airway. The  SCGB1A1  gene has been characterized in mammals as a single copy in the genome. However, analysis of the equine genome suggested that horses might have multiple  SCGB1A1  gene copies. Non-ciliated lung epithelial cells produce SCGB 1A1 during inhalation of noxious substances to counter airway inflammation. Airway fluid and lung tissue of horses with recurrent airway obstruction (RAO), a chronic inflammatory lung disease affecting mature horses similar to environmentally induced asthma of humans, have reduced total SCGB 1A1 concentration. Herein, we investigated whether horses have distinct expressed  SCGB1A1  genes; whether the transcripts are differentially expressed in tissues and in inflammatory lung disease; and whether there is cell specific protein expression in tissues.    Results  We identified three  SCGB1A1  gene copies on equine chromosome 12, contained within a 512-kilobase region. Bioinformatic analysis showed that  SCGB1A1  genes differ from each other by 8 to 10 nucleotides, and that they code for different proteins. Transcripts were detected for  SCGB1A1  and  SCGB1A1A , but not for  SCGB1A1P . The  SCGB1A1P  gene had most inter-individual variability and contained a non-sense mutation in many animals, suggesting that  SCGB1A1P  has evolved into a pseudogene. Analysis of  SCGB1A1  and  SCGB1A1A  sequences by endpoint-limiting dilution PCR identified a consistent difference affecting 3 bp within exon 2, which served as a gene-specific “signature”. Assessment of gene- and organ-specific expression by semiquantitative RT-PCR of 33 tissues showed strong expression of  SCGB1A1  and  SCGB1A1A  in lung, uterus, Fallopian tube and mammary gland, which correlated with detection of SCGB 1A1 protein by immunohistochemistry. Significantly altered expression of the ratio of  SCGB1A1A  to  SCGB1A1  was detected in RAO-affected animals compared to controls, suggesting different roles for SCGB 1A1 and SCGB 1A1A in this inflammatory condition.    Conclusions  This is the first report of three  SCGB1A1  genes in a mammal. The two expressed genes code for proteins predicted to differ in function. Alterations in the gene expression ratio in RAO suggest cell and tissue specific regulation and functions. These findings may be important for understanding of lung and reproductive conditions.

Multiple secretoglobin 1A1 genes are differentially expressed in horses