Altered expression of genes functioning in lipid homeostasis is associated with lipid deposition in NOD mouse lacrimal gland

• Main Authors: Wu , Kaijin (University of Southern California(Etats-Unis). Department of Pharmacology and Pharmaceutical Sciences), Joffre , Corinne(auteur de correspondance) (INRA , DijonBordeaux (France). UMRUMR 11291286 Flaveur, Vision et Comportement du ConsommateurUnité de Psychoneuroimmunologie, Nutrition et Génétique), Xiaodong Li , X.L. (University of Southern California(Etats-Unis). Department of Pharmacology and Pharmaceutical Sciences), MacVeigh-Aloni , Michelle (University of Southern California(Etats-Unis). Center for Liver Diseases), Hom , Melinda (University of Southern California(Etats-Unis). Department of Pharmacology and Pharmaceutical Sciences), Hwang , Juliana (University of Southern California(Etats-Unis). Department of Pharmacology and Pharmaceutical Sciences), Chuanqing Ding , C.D. (University of Southern California(Etats-Unis). Department of Pathology and Neurology), Grégoire , Stéphane (INRA , Dijon (France). UMR 1129 Flaveur, Vision et Comportement du Consommateur), Bretillon , Lionel (INRA , Dijon (France). UMR 1129 Flaveur, Vision et Comportement du Consommateur), Zong , ZhJiang F. (University of Southern California(Etats-Unis). Department of Pathology and Neurology), Hamm-Alvarez , Sarah F. (University of Southern California(Etats-Unis). Department of Pharmacology and Pharmaceutical Sciences)
• Format: Publication
• Language: English
• Published: 2009
• Subjects: APOLIPOPROTEIN E; APOLIPOPROTEIN F; LACRIMAL GLAND; LIPID; MICRARRAY; NOD MOUSE; SJÖGREN'S SYNDROME

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.