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Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity
Published on: January 6, 2015
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Transcriptomic analysis comparing mouse strains with extreme total lung capacities identifies novel candidate genes
Leema George1, Ankita Mitra1, Tania A Thimraj1
1SRM Research Institute, SRM University, Chennai, 603203, India.
Respiratory Research
|August 11, 2017
Summary
This study identified novel genes influencing lung function by comparing transcriptomes in mice with different total lung capacities (TLCs). These findings offer new insights into early lung development and disease risk.
Area of Science:
- Pulmonary Medicine
- Genetics
- Developmental Biology
Background:
- Failure to achieve peak lung function in adulthood is a risk factor for chronic lung diseases.
- C3H/HeJ mice exhibit approximately twice the total lung capacity (TLC) of JF1/MsJ mice.
- Previous work identified seven lung function quantitative trait loci (QTL) and genes like Sod3, Kit, and Spp1 as lung function determinants.
Purpose of the Study:
- To identify novel candidate genes for pulmonary function.
- To investigate the lung transcriptome in C3H/HeJ and JF1/MsJ mice at key developmental stages (embryonic, alveolar formation, maturity).
- To understand the early origins of lung disease by examining gene expression differences related to lung function.
Main Methods:
- Design-based stereological analysis of lung structure in C3H/HeJ and JF1/MsJ mice.
- Microarray analysis of lung transcriptomes at embryonic day 18, postnatal days 28, and 70.
- Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemical analysis to validate gene expression differences.
Main Results:
- Stereological analysis showed decreased alveolar number density and elastin to collagen ratio, with increased mean alveolar volume in C3H/HeJ mice.
- The gene ontology term "extracellular region" was enriched among downregulated transcripts in JF1/MsJ mice.
- Identified candidate genes include Abcg1, Fpr1, Gabbr1, H2-Eb1, H2-D1, H2-Q4, Lrrc6, Rsph1, Sfta2, Wif1, Fst, Chil1, and Chil3.
Conclusions:
- Comparison of lung transcript profiles across development identified novel candidate genes for pulmonary function.
- These findings contribute to understanding genetic determinants of lung function and early lung disease.
- Further research is needed to elucidate the precise mechanisms of these candidate genes in determining lung function.
