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

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‐re...

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Veröffentlicht in:American journal of primatology 2001-06, Vol.54 (2), p.107-118
Hauptverfasser: Chun, Rene F., Chen, Hong, Boldrick, Lorrie, Sweet, Connie, Adams, John S.
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container_end_page 118
container_issue 2
container_start_page 107
container_title American journal of primatology
container_volume 54
creator Chun, Rene F.
Chen, Hong
Boldrick, Lorrie
Sweet, Connie
Adams, John S.
description 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. © 2001 Wiley‐Liss, Inc.
doi_str_mv 10.1002/ajp.1016
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J. Primatol</addtitle><description>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. 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J. Primatol</addtitle><date>2001-06</date><risdate>2001</risdate><volume>54</volume><issue>2</issue><spage>107</spage><epage>118</epage><pages>107-118</pages><issn>0275-2565</issn><eissn>1098-2345</eissn><coden>AJPTDU</coden><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. © 2001 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>11376448</pmid><doi>10.1002/ajp.1016</doi><tpages>12</tpages></addata></record>
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subjects Amino Acid Sequence
Animals
Antibody Specificity
Base Sequence
Biological and medical sciences
Biology
Blotting, Western - veterinary
cDNA
Cell Line, Transformed
Cell receptors
Cell structures and functions
Cercopithecus aethiops
Cloning
Cloning, Molecular
cotton top tamarin
DNA - genetics
Fundamental and applied biological sciences. Psychology
Genetics
hormone resistance
Humans
Miscellaneous
Molecular and cellular biology
Molecular Sequence Data
New World monkeys
New World primates
platyrrhini
Primates
Primatology
Receptors, Calcitriol - genetics
Receptors, Calcitriol - immunology
Receptors, Calcitriol - physiology
Resistance
Reverse Transcriptase Polymerase Chain Reaction - veterinary
rickets
Saguinus - genetics
Saguinus - physiology
Scientific research
Sequence Alignment
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Transcriptional Activation
Transfection - veterinary
Vitamin D - physiology
vitamin D receptor
vitamin D receptors
vitamin D resistance
Vitamin D-Binding Protein - physiology
title Cloning, sequencing, and functional characterization of the vitamin D receptor in vitamin D-resistant New World primates
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