Figure 4.

Transgenic (TG) expression of VDR specifically in ileum, cecum, and colon of VDR null mice prevents the abnormal calcium phenotype of VDR null mice. A: the full-length hVDR cDNA was introduced into the multiple cloning cassette under control of the 9.5-kb CDX2 promoter region (9.5 kb CDX2 from E. Fearon). Mice expressing VDR exclusively in the ileum, cecum, and colon were generated by breeding VDR null mice with TG mice expressing hVDR under the control of 9.5-kb CDX2. B, top panel: expression of hVDR was restricted to ileum, cecum, and colon. Mouse (m) VDR was present in WT but not in TG mice or VDR null (KO) mice. Levels of VDR in the distal intestine in TG mice were equivalent or 1.5 upregulated compared with WT. Bottom panel: Van Kossa staining of histolocial sections of tibia showing that the expression of hVDR in the distal intestine (KO/TG1 and KO/TG2) rescues the bone defects associated with systemic VDR deficiency. Serum PTH and serum calcium are normalized in KO/TG1 and KO/TG2 mice (not shown). [From Dhawan et al. (112).]