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Global Gene Profiling of Aging Lungs in Atp8b1 Mutant Mice

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Specialty Geriatrics
Date 2016 Oct 1
PMID 27689529
Citations 8
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Abstract

Objective: Recent studies implicate cardiolipin oxidation in several age-related diseases. encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between mutation and age-related gene alteration is unknown. Therefore, we investigated how 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 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 lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes in lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase in and transcripts in aged lungs was validated by qRT-PCR. Similarly, the decrease in and increase in transcripts was confirmed in both mutant and C57BL/6 lungs.

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

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