Transgenic expression of the human Vitamin D receptor (hVDR) in the duodenum of VDR-null mice attenuates the age-dependent decline in calcium absorption.

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Marks HD, Fleet JC, Peleg S

Transgenic expression of the human Vitamin D receptor (hVDR) in the duodenum of VDR-null mice attenuates the age-dependent decline in calcium absorption.

J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):513-6. Epub 2007 Jan 5.

PubMed ID

17207992 [ View in PubMed

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Abstract

1,25(OH)(2)D(3) regulates calcium homeostasis through its actions in the intestine, bone, and kidney. These actions are mediated through the VDR. To determine if VDR's actions in the proximal small intestine can sufficiently restore calcium homeostasis, we generated transgenic mice expressing hVDR exclusively in the duodenum of mVDR-null mice by using the adenosine deaminase enhancer (hVDR+/mVDR-null). Unlike wild-type mice, hVDR+/mVDR-null mice express hVDR and VDR target genes only in the proximal small intestine. Despite having functional hVDR in the proximal small intestine, hVDR+/mVDR-null mice were hypocalcaemic when fed a normal rodent diet at weaning, like mVDR-null mice fed the same diet. The hypocalcemia in these mice is prevented if they are given the rescue diet before weaning. However, when 90-day-old rachitic mice were fed a rescue diet, serum calcium improved in hVDR+/mVDR-null mice, but not in mVDR-null mice. In conclusion, transgenic hVDR in the proximal small intestine of hVDR+/mVDR-null mice was transcriptionally active and regulated calcium absorption, but VDR actions elsewhere in the intestine are probably necessary to support adequate calcium homeostasis. In addition, hVDR+/mVDR-null mice responded better to the late rescue diet suggesting that expression of VDR in the proximal small intestine protected the calcium absorbing machinery from age-dependent decline.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ergocalciferol	Vitamin D3 receptor	Protein	Humans	Yes	Agonist	Details