Partial Rescue of the Phenotype in 1 alpha-Hydroxylase Gene Knockout Mice by Vitamin D3 Injection

Objective: To investigate whether 25-hydroxyvitamin D [25(OH)D] can mediate effects without being converted to 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D]. Methods: Vitamin D3 (VD3) was injected intramuscularly to 25-hydroxyvitamin D-1 alpha-hydroxylase [1 alpha(OH)ase] gene knockout (KO) male mice with a dose of 10,000 IU per week for 4 weeks. Skeleton Parameters and Serum biochemistry in mice were assayed. Results: Serum 25(OH) D3 levels increased from 41 to 212 ng/mL in KO mice injected with VD3. Our results show that VD3 injections significantly increased the body weight of KO mice and there were no significant differences in body weight at 7 weeks of age between VD3-treated KO mice and wildtype (WT) mice. After 1 month injection, serum calcium and phosphorus levels of the KO mice were found indistinguishable from those of their WT littermates. Serum parathyroid hormone level declined significantly, but remained higher in treated KO mice. The dry weight, percentage ash weight, and calcium content of femur were returned to normal levels in VD3-treated KO mice whereas the femoral length, although increased significantly, remained significantly smaller than that of WT mice. VD3 injections also normalized the growth plate of KO mice within normal width. Conclusions: Our results demonstrate that high-dose VD3 injections can partially rescue the phenotype in 1 alpha-hydroxylase gene KO mice. 25-Hydroxyvitamin D can mediate effects in the absence of conversion to 1 alpha,25-dihydroxyvitamin D was confirmed in this study.