Systematic analysis of candidate reference genes for gene expression analysis in hyperoxia-based mouse models of bronchopulmonary dysplasia

Am J Physiol Lung Cell Mol Physiol. 2021 Oct 1;321(4):L718-L725. doi: 10.1152/ajplung.00143.2021. Epub 2021 Aug 11.

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants. Mouse models of hyperoxia-induced lung injury are often used to study pathogenesis and potential therapeutic approaches of BPD. Beside histological studies, gene expression analysis of lung tissue is typically used as experimental readout. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) is the standard method for gene expression analysis; however, the accuracy of the quantitative data depends on the appropriate selection of reference genes. No data on validated reference genes for hyperoxia-induced neonatal lung injury in mice are available. In this study, 12 potential reference genes were systematically analyzed for their expression stability in lung tissue of neonatal mice exposed to room air or hyperoxia and healthy adult controls using published software algorithms. Analysis of gene expression data identified Hprt, Tbp, and Hmbs as the most stable reference genes and proposed combinations of Hprt/Sdha or Hprt/Rpl13a as potential normalization factors. These reference genes and normalization factors were validated by comparing Il6 gene and protein expression and may facilitate accurate gene expression analysis in lung tissues of similar designed studies.

Keywords: bronchopulmonary dysplasia; housekeeping genes; hyperoxia mouse model; reference genes; validation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bronchopulmonary Dysplasia / genetics*
  • Bronchopulmonary Dysplasia / pathology
  • Cytokines / analysis
  • Disease Models, Animal
  • Electron Transport Complex II / genetics*
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Hyperoxia / pathology
  • Hypoxanthine Phosphoribosyltransferase / genetics*
  • Lung / pathology
  • Lung Injury / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxygen / pharmacology
  • Real-Time Polymerase Chain Reaction
  • Ribosomal Proteins / genetics*
  • Signal Transduction / genetics
  • TATA-Box Binding Protein / genetics*

Substances

  • Cytokines
  • Ribosomal Proteins
  • Rpl13a protein, mouse
  • TATA-Box Binding Protein
  • Electron Transport Complex II
  • Hypoxanthine Phosphoribosyltransferase
  • Oxygen

Associated data

  • figshare/10.6084/m9.figshare.15043062