Global gene profiling of aging lungs in Atp8b1 mutant mice.
Recent studies implicate cardiolipin oxidation in several age-related diseases.Atp8b1encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation inAtp8b1gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link betweenAtp8b1mutation and age-related gene alteration is unknown. Therefore, we investigated howAtp8b1mutation alters age-related genes.



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 andAtp8b1mutant mice. In addition, Ingenuity Pathway Analysis (IPA) was performed. Differentially expressed genes were validated by quantitative real-time PCR (qRT-PCR).



Global transcriptome analysis revealed 532 differentially expressed genes inAtp8b1lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes inAtp8b1lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase inAdamts2andMmp13transcripts in agedAtp8b1lungs was validated by qRT-PCR. Similarly, the decrease inCol1a1and increase inCxcr6transcripts was confirmed in bothAtp8b1mutant and C57BL/6 lungs.



Based on transcriptome profiling, our study indicates thatAtp8b1mutant mice may be susceptible to age-related lung diseases.
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Ramani
R
Soundararajan
MDI Biological Laboratory, Salisbury Cove, ME 04672, USA.
Timothy M
TM
Stearns
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Alexander
A
Czachor
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Jutaro
J
Fukumoto
University of Florida College of Medicine, Gainesville, FL 32608, USA.
Christina
C
Turn
Division of Allergy and Immunology, Department of Internal Medicine, James A Haley Veterans Hospital, Tampa, FL 33612, USA.
Emma
E
Westermann-Clark
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Mason
M
Breitzig
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Lee
L
Tan
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Richard F
RF
Lockey
MDI Biological Laboratory, Salisbury Cove, ME 04672, USA.
Benjamin L
BL
King
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Narasaiah
N
Kolliputi
D000071096:ADAMTS Proteins / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D020869:Gene Expression Profiling; D008168:Lung / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D049294:Phospholipid Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
D049294:Phospholipid Transfer Proteins; D000071096:ADAMTS Proteins; D053509:Matrix Metalloproteinase 13; C000609308:Adamts2 protein, mouse; D000251:Adenosine Triphosphatases; C491742:Atp8b1 protein, mouse
Atp8b1 mutant; aging; gene profiling; lungs; transcriptome
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