Title: Unaltered diabetes presentation in NOD mice lacking the vitamin D receptor
Authors: Gysemans, Conny
van Etten, Evelyne
Overbergh, Lutgart
Giulietti, Annapaula
Eelen, Guy
Waer, Mark
Verstuyf, Annemieke
Bouillon, Roger
Mathieu, Chantal # ×
Issue Date: Jan-2008
Series Title: Diabetes vol:57 issue:1 pages:269-275
Abstract: OBJECTIVE: Vitamin D deficiency increases risk for type 1 diabetes in genetically predisposed individuals, while high doses of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] prevent insulitis and diabetes in NOD mice. RESEARCH DESIGN AND METHODS: Since 1,25(OH)(2)D(3) regulates gene transcription through the vitamin D receptor (VDR), we investigated the role of VDR in diabetes development by creating NOD mice without functional VDR. RESULTS: VDR(-/-) NOD mice are rachitic and have lower numbers of putative regulator cells [TCR-alpha/beta(+)CD4(-)CD8(-) (natural killer T-cells) and CD4(+)CD25(+) T-cells [in central and peripheral immune organs compared with VDR(+/+) NOD littermates. Lipopolysaccharide-stimulated VDR(-/-) NOD macrophages expressed lower interleukin (IL)-1, IL-6, and CC chemokine ligand 2 mRNA, correlating with less nuclear translocation of p65 nuclear factor-kappaB compared with VDR(+/+) NOD macrophages. Thymic and lymph node dendritic cells from VDR(-/-) NOD mice displayed an even less mature CD11c(+)CD86(+) phenotype than VDR(+/+) NOD mice. Despite this immune phenotype linked to diabetes in NOD mice, VDR(-/-) NOD mice developed insulitis and diabetes at the same rate and incidence as VDR(+/+) NOD littermates. CONCLUSIONS: Despite aggravating known immune abnormalities in NOD mice, disruption of VDR does not alter disease presentation in NOD mice in contrast to the more aggressive diabetes presentation in vitamin D-deficient NOD mice.
ISSN: 0012-1797
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Laboratory of Nephrology
Laboratory of Experimental Transplantation
× corresponding author
# (joint) last author

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