PMID- 10423037
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190905
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 25
IP  - 1
DP  - 1999 Jul
TI  - Targeted inactivation of vitamin D hydroxylases in mice.
PG  - 127-9
AB  - Vitamin D undergoes a first hydroxylation in the liver to generate
      25-hydroxyvitamin D, then this metabolite is further hydroxylated in the kidney
      to yield either 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D], or
      24R,25-dihydroxyvitamin D[24,25(OH)2D]. The production of 1alpha,25(OH)2D is
      catalyzed by the enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase),
      while the synthesis of 24,25(OH)2D is catalyzed by the enzyme 25-hydroxyvitamin
      D-24-hydroxylase (24-OHase). To determine the role of each of these enzymes in
      vivo and their putative role during development, we have inactivated each gene by
      homologous recombination in embryonic stem cells. The targeting vector for the
      1alpha-OHase gene was constructed to allow tissue-specific gene inactivation in
      order to study the hypothesized paracrine/autocrine roles of the 1alpha-OHase
      enzyme in particular target tissues such as skin, brain, or macrophages. The
      targeting vector for the 24-OHase gene utilized standard methodology, and
      analysis of the phenotype of 24-OHase-deficient mice confirmed the role of the
      24-OHase enzyme in the catabolism of 1alpha,25(OH)2D. The phenotype of the second
      generation 24-OHase-null mice also suggests a key role for 24,25(OH)2D in
      intramembranous bone formation during development.
FAU - St-Arnaud, R
AU  - St-Arnaud R
AD  - Shriners Hospital for Children, and Department of Surgery, McGill University,
      Montreal, Quebec, Canada. rst-arnaud@shriners.mcgill.ca
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 1406-16-2 (Vitamin D)
RN  - EC 1.14.- (Steroid Hydroxylases)
SB  - IM
MH  - Animals
MH  - Bone Development/physiology
MH  - Embryonic and Fetal Development/physiology
MH  - Genetic Engineering
MH  - Mice
MH  - Phenotype
MH  - Steroid Hydroxylases/*metabolism
MH  - Vitamin D/*metabolism
RF  - 21
EDAT- 1999/07/28 00:00
MHDA- 1999/07/28 00:01
CRDT- 1999/07/28 00:00
PHST- 1999/07/28 00:00 [pubmed]
PHST- 1999/07/28 00:01 [medline]
PHST- 1999/07/28 00:00 [entrez]
AID - S8756-3282(99)00118-0 [pii]
AID - 10.1016/s8756-3282(99)00118-0 [doi]
PST - ppublish
SO  - Bone. 1999 Jul;25(1):127-9. doi: 10.1016/s8756-3282(99)00118-0.