Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2001-6-20
pubmed:abstractText
The active form of vitamin D, 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D], is synthesized from its precursor 25 hydroxyvitamin D [25(OH)D] via the catalytic action of the 25(OH)D-1alpha-hydroxylase [1alpha(OH)ase] enzyme. Many roles in cell growth and differentiation have been attributed to 1,25(OH)2D, including a central role in calcium homeostasis and skeletal metabolism. To investigate the in vivo functions of 1,25(OH)2D and the molecular basis of its actions, we developed a mouse model deficient in 1alpha(OH)ase by targeted ablation of the hormone-binding and heme-binding domains of the 1alpha(OH)ase gene. After weaning, mice developed hypocalcemia, secondary hyperparathyroidism, retarded growth, and the skeletal abnormalities characteristic of rickets. These abnormalities are similar to those described in humans with the genetic disorder vitamin D dependent rickets type I [VDDR-I; also known as pseudovitamin D-deficiency rickets (PDDR)]. Altered non-collagenous matrix protein expression and reduced numbers of osteoclasts were also observed in bone. Female mutant mice were infertile and exhibited uterine hypoplasia and absent corpora lutea. Furthermore, histologically enlarged lymph nodes in the vicinity of the thyroid gland and a reduction in CD4- and CD8-positive peripheral T lymphocytes were observed. Alopecia, reported in vitamin D receptor (VDR)-deficient mice and in humans with VDDR-II, was not seen. The findings establish a critical role for the 1alpha(OH)ase enzyme in mineral and skeletal homeostasis as well as in female reproduction and also point to an important role in regulating immune function.
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7498-503
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:11416220-25-Hydroxyvitamin D3 1-alpha-Hydroxylase, pubmed-meshheading:11416220-Animals, pubmed-meshheading:11416220-Bone Diseases, pubmed-meshheading:11416220-Calcifediol, pubmed-meshheading:11416220-Calcitriol, pubmed-meshheading:11416220-Calcium, pubmed-meshheading:11416220-Disease Models, Animal, pubmed-meshheading:11416220-Female, pubmed-meshheading:11416220-Growth Disorders, pubmed-meshheading:11416220-Heterozygote, pubmed-meshheading:11416220-Homozygote, pubmed-meshheading:11416220-Humans, pubmed-meshheading:11416220-Hyperparathyroidism, pubmed-meshheading:11416220-Infertility, Female, pubmed-meshheading:11416220-Male, pubmed-meshheading:11416220-Mice, pubmed-meshheading:11416220-Mice, Knockout, pubmed-meshheading:11416220-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11416220-Rickets
pubmed:year
2001
pubmed:articleTitle
Targeted ablation of the 25-hydroxyvitamin D 1alpha -hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction.
pubmed:affiliation
Calcium Research Laboratory, Royal Victoria Hospital, McGill University, Montreal, QC, Canada H3A 1A1.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't