Vitamin D exerts a wide variety of biological actions. The active form of vitamin D, 1α,25(OH)2D3, is biosynthesized from cholesterol. The final, critical step in this biosynthesis is conversion from 25-hydroxyvitamin D3 to 1α,25(OH)2D3 by the enzyme 25-hydroxyvitamin D3 1α-hydroxylase(CYP27B1)[1α(OH)ase]. 1α,25(OH)2D3 transcriptionally controls the expression of a particular set of target genes mediated through nuclear vitamin D receptor(VDR) acting as a ligand-inducible factor. Two types of vitamin D-dependent hereditary rickets (VDDR) are known to be caused by mutations in the 1α(OH)ase and VDR genes. The 1α(OH)ase gene is responsible for VDDR type I, and VDR for type II. Both of the diseases display an autosomal-recessive trait, but clinical features and response to administrated 1α,25(OH)2D3 are distinct. The phenotypes of the gene KO mice deficient of 1α(OH)ase and VDR exhibited the clinical abnormalities observed in the VDDR patients.

Keywords:
Hereditary rickets, Vitamin D, Vitamin D receptor, Vitamin D1 alpha-hydroxylase, Vitamin D receptor KO mice
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