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J.L. Ubels, H.E. Shaffer, C.P. Webb; Gene Expression in Lacrimal Gland Secretory Cells of MRL/lpr Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3532.
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The MRL/lpr mouse has been used for many years as a model for the lymphocytic infiltration of the lacrimal gland that occurs in Sjogren’s syndrome. Most of these studies have focused on the inflammatory cells that infiltrate the gland, but little is known about the characteristics of acinar and duct cells of the inflamed gland, which may have intrinsic abnormalities that disrupt the function of these cells. The overall goal of this study was to compare gene expression in acinar and duct cells of MRL/lpr and control BALB–c mice collected by laser capture microdissection (LCM).
RNA was extracted from acinar and duct cells of 6 female MRL/lpr mice with stage 0 or stage 3–4 lymphocytic infiltration and from cells of 6 age–matched female BALB/c mice. Reference standard RNA was prepared from 13–day mouse embryos. The RNA was amplified, reverse transcribed with Cy3 or Cy5 dCTP and hybridized to 12000 gene mouse cDNA microarrays.
Assuming that within cell type similarities would be greater than differences between diseased and normal cells, ducts were compared to acinar cells without regard to disease state or age of the animals. Cluster analysis provided evidence for genomic distinction between ducts and acini. Among the genes that were the top discriminators between ducts and acini were Ro/SSA antigen (Trim21) and lactoferrin (Lft) which were expressed more highly in ducts. MRL and normal glands were compared using pooled duct and acinar microarrays, and by comparison of acini alone between normal and diseased mice. Cluster analysis correctly classified the MRL and control animals, confirming differences in genotype between the disease strain and normal mice. MRL/lpr mice with stage 0 lacrimal disease were classified separately from older mice with stage 3–4 disease suggesting a change in genotype between the early and late disease states. Top discriminators between MRL and normal mice included lymphocyte antigen 6 complex, locus E (Ly6e) and locus A (Ly6a), Stat3, fibrillarin (Fbl) (a nucleolar autoantigen expressed in scleroderma) and histocompatibility complex II antigen (H2–Eb1), all increased in MRL mice, and eukaryotic translation initiation factor 4E (Eif4e) (a gene inhibited by inflammation and stress) which was down–regulated in MRL mice.
The data suggest differences in gene expression in lacrimal secretory cells between MRL/lpr and normal mice. The strength of the analysis is the use of LCM to analyze the cells without the presence of RNA from inflammatory cells. Expression of several genes with important relationships to Sjogren’s syndrome was detected.
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