Abstract: 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.
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The research paper is focused on exploring the expression of Secretoglobin 1A1 genes, also known as SCGB 1A1, in horses and their differential expression as it relates to tissue-specific, inflammatory lung diseases such as Recurrent Airway Obstruction (RAO).
Study Overview
The study’s objective was to investigate the presence and expression of the SCGB1A1 genes in horses. These genes, which had previously been identified as a single copy in mammalian genome, are associated with the production of SCGB 1A1, a protein that helps counteract airway inflammation.
Suspecting multiple copies of these genes might exist in horses, researchers carried out a bioinformatic analysis which led to the discovery of three SCGB1A1 gene copies on equine chromosome 12.
The team subsequently sought to understand whether the multiple SCGB1A1 genes expressed different transcripts, if the genes’ expressions varied based on tissue and disease state, and how their protein expressions were distributed across tissues.
Key Findings
The study identified three copies of the SCGB1A1 gene, differing from each other by 8 to 10 nucleotides and coding for different proteins. These were found on equine chromosome 12 within a 512-kb region.
From the three identified genes, transcripts for SCGB1A1 and SCGB1A1A were detected, while SCGB1A1P showed none. The SCGB1A1P also had the most inter-individual variability and had many instances of non-sense mutations, indicating that it had likely evolved into a pseudogene.
Further analysis found a consistent 3 bp difference within exon 2, acting as a gene-specific “signature”.
RT-PCR of 33 tissues demonstrated strong expression of SCGB1A1 and SCGB1A1A in the lung, uterus, Fallopian tube, and mammary gland, correlating with the detection of the SCGB 1A1 protein via immunohistochemistry.
In horses affected by RAO, significant alterations in the expression ratio of SCGB1A1A to SCGB1A1 were observed compared to healthy controls. This finding suggests that these two genes may play different roles in the inflammatory condition.
Study Conclusions
The research study provided the first report of mammals (the horses in this case) having more than one SCGB1A1 gene. Additionally, the two expressed genes were predicted to differ in function.
The alterations in gene expression in RAO-affected horses suggest the possibility of tissue and cell-specific regulation and functions for the SCGB1A1 genes.
These findings could potentially provide insights into the understanding and treatment of lung and reproductive conditions.
Cite This Article
APA
Côté O, Lillie BN, Hayes MA, Clark ME, van den Bosch L, Katavolos P, Viel L, Bienzle D.
(2012).
Multiple secretoglobin 1A1 genes are differentially expressed in horses.
BMC Genomics, 13, 712.
https://doi.org/10.1186/1471-2164-13-712
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