Abstract
Vitamin D exerts various physiological functions such as osteogenesis, antitumor and immunomodulatory effects, all of which are intimately involved in health promotion. The canonical molecular pathway of vitamin D involves the binding of 1,25-dihydroxyvitamin D3 (1α,25(OH) 2D3), an active form of vitamin D, to the vitamin D receptor (VDR). In addition to the existing mechanism of vitamin D, however, novel molecular mechanisms underlying the functions of vitamin D, including the VDR-independent action of 1α,25(OH) 2D3 and a direct action of 25-hydroxyvitamin D3 (25(OH)D3, a precursor of 1α,25(OH) 2D3), has been reported recently. Further elucidation of the mechanisms for these novel functions of vitamin D may bring a useful information for new drug discovery targets and health promotion strategies. In order to elucidate the molecular mechanisms for novel physiological functions of vitamin D in vivo, we generated several animal models of rickets in which vitamin D-related genes, such as Cyp27b1 and Vdr, have been inactivated by the genetic engineering method. This review aims to introduce our findings obtained from comparative phenotypic studies using these animal models of rickets and to show the usefulness of these animal models for vitamin D-related research.
