Altered expression of genes functioning in lipid homeostasis is associated with lipid deposition in NOD mouse lacrimal gland
Experimental Eye Research. 2009-09-01; 89(3): 319-332
DOI: 10.1016/j.exer.2009.03.020
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1. Exp Eye Res. 2009 Sep;89(3):319-32. doi: 10.1016/j.exer.2009.03.020. Epub 2009
Apr 2.
Altered expression of genes functioning in lipid homeostasis is associated with
lipid deposition in NOD mouse lacrimal gland.
Wu K(1), Joffre C, Li X, MacVeigh-Aloni M, Hom M, Hwang J, Ding C, Gregoire S,
Bretillon L, Zhong JF, Hamm-Alvarez SF.
Author information:
(1)Department of Pharmacology and Pharmaceutical Sciences, University of Southern
California, CA 90089, USA.
Functional atrophy and accompanying lymphocytic infiltration and destruction of
the lacrimal gland (LG) are characteristics of Sjögren’s Syndrome (SjS). The male
NOD mouse is an experimental model for the autoimmune exocrinopathy that develops
in the LG of SjS patients. Acinar cells in LG of male NOD mice aged 3-4 months
were previously shown to accumulate lipid droplets. In the current study,
analysis of lipid components revealed that the accumulated lipids were mostly
cholesteryl esters (CE). Gene expression microarray analysis followed by
real-time RT-PCR revealed alterations in the expression of several genes involved
in lipid homeostasis in LG of 12-week-old male NOD mice relative to matched
BALB/c controls. A series of upregulated genes including apolipoprotein E,
apolipoprotein F, hepatic lipase, phosphomevalonate kinase, ATP-binding cassette
D1 and ATP-binding cassette G1 were identified. Comparison of liver mRNAs to LG
mRNAs in BALB/c and NOD mice revealed that the differential expressions were
LG-specific. Gene expression profiles were also characterized in LGs of female
mice, younger mice and immune-incompetent NOD SCID mice. Investigation of the
cellular distribution of Apo-E and Apo-F proteins suggested that these proteins
normally coordinate to mediate lipid efflux from the acinar cells but that
dysfunction of these processes due to missorting of Apo-F may contribute to CE
deposition. Finally, the initiation and extent of lipid deposition were
correlated with lymphocytic infiltration in the LG of male NOD mice. We propose
that impaired lipid efflux contributes to lipid deposition, an event that may
contribute to the development and/or progression of dacryoadenitis in the male
NOD mouse.
DOI: 10.1016/j.exer.2009.03.020
PMCID: PMC2720431
PMID: 19345210 [Indexed for MEDLINE]