Global gene profiling of aging lungs in Atp8b1 mutant mice

Aging (Albany NY). 2016 Sep 29;8(9):2232-2252. doi: 10.18632/aging.101056.


Objective: Recent studies implicate cardiolipin oxidation in several age-related diseases. Atp8b1 encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in Atp8b1 gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between Atp8b1 mutation and age-related gene alteration is unknown. Therefore, we investigated how Atp8b1 mutation alters age-related genes.

Methods: We performed Affymetrix gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months, 14 M, n=6) C57BL/6 and Atp8b1 mutant mice. In addition, Ingenuity Pathway Analysis (IPA) was performed. Differentially expressed genes were validated by quantitative real-time PCR (qRT-PCR).

Results: Global transcriptome analysis revealed 532 differentially expressed genes in Atp8b1 lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes in Atp8b1 lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase in Adamts2 and Mmp13 transcripts in aged Atp8b1 lungs was validated by qRT-PCR. Similarly, the decrease in Col1a1 and increase in Cxcr6 transcripts was confirmed in both Atp8b1 mutant and C57BL/6 lungs.

Conclusion: Based on transcriptome profiling, our study indicates that Atp8b1 mutant mice may be susceptible to age-related lung diseases.

Keywords: Atp8b1 mutant; aging; gene profiling; lungs; transcriptome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAMTS Proteins / genetics
  • ADAMTS Proteins / metabolism
  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Gene Expression Profiling
  • Lung / metabolism*
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Mice
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Phospholipid Transfer Proteins / genetics*
  • Phospholipid Transfer Proteins / metabolism
  • Transcriptome


  • Phospholipid Transfer Proteins
  • ADAMTS Proteins
  • Matrix Metalloproteinase 13
  • Adamts2 protein, mouse
  • Adenosine Triphosphatases
  • Atp8b1 protein, mouse