Cloning, sequencing, and functional characterization of the vitamin D receptor in vitamin D‐resistant New World primates

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Abstract
New World primates (NWPs) have high circulating 1,25‐dihydroxyvitamin D (1,25‐(OH)2D) levels. Comparable levels would be harmful to Old World primates (OWPs) and humans. Thus, NWPs must have developed mechanisms of 1,25‐(OH)2D resistance to survive. In humans, patients with hypocalcemic vitamin D‐resistant rickets type II have high circulating vitamin D levels and vitamin D resistance due to expression of a dysfunctional vitamin D receptor (VDR). To examine if this could wholly or in part explain vitamin D resistance in NWPs, VDR from Saguinus oedipus (cotton top tamarin) NWP B95‐8 cells was cloned by reverse‐transcription polymerase chain reaction (RT‐PCR). The NWP VDR cDNA sequence showed 96% homology at the DNA level and 98% homology at the amino acid level compared to human VDR. To assay for function, NWP VDR cDNA was transiently transfected into CV‐1 cells with a vitamin D response element reporter plasmid. No difference between OWP and NWP VDR‐directed transactivation was observed. These results indicate that the mechanism of vitamin D resistance in NWPs is not due to a dysfunctional VDR, and is consistent with our hypothesis that vitamin D resistance in NWPs is mediated by overexpression of a VDR‐independent vitamin D response element binding protein. Am. J. Primatol. 54:107–118, 2001.