PMID- 17207992
OWN - NLM
STAT- MEDLINE
DCOM- 20070511
LR  - 20161124
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 103
IP  - 3-5
DP  - 2007 Mar
TI  - Transgenic expression of the human Vitamin D receptor (hVDR) in the duodenum of 
      VDR-null mice attenuates the age-dependent decline in calcium absorption.
PG  - 513-6
AB  - 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.
FAU - Marks, Hilary D
AU  - Marks HD
AD  - Department of Endocrine Neoplasia and Hormonal Disorders, Unit 435, The 
      University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Fleet, James C
AU  - Fleet JC
FAU - Peleg, Sara
AU  - Peleg S
LA  - eng
GR  - R01 DK054111-11A1/DK/NIDDK NIH HHS/United States
GR  - R01 DK054111/DK/NIDDK NIH HHS/United States
GR  - DK 50583/DK/NIDDK NIH HHS/United States
GR  - R01 DK050583/DK/NIDDK NIH HHS/United States
GR  - DK 54111/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070105
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.15.16 (Vitamin D3 24-Hydroxylase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Calcium/*blood
MH  - Duodenum/*metabolism
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Receptors, Calcitriol/*deficiency/genetics/*metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Steroid Hydroxylases/genetics
MH  - Vitamin D3 24-Hydroxylase
EDAT- 2007/01/09 09:00
MHDA- 2007/05/12 09:00
CRDT- 2007/01/09 09:00
PHST- 2007/01/09 09:00 [pubmed]
PHST- 2007/05/12 09:00 [medline]
PHST- 2007/01/09 09:00 [entrez]
AID - S0960-0760(06)00351-7 [pii]
AID - 10.1016/j.jsbmb.2006.11.014 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):513-6. doi: 
      10.1016/j.jsbmb.2006.11.014. Epub 2007 Jan 5.