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Journal Articles Endocrinology Year : 2001

Aberrant Growth Plate Development in VDR/RXRγ Double Null Mutant Mice

Naoko Yagishita
  • Function : Author
Yoko Yamamoto
  • Function : Author
Tatsuya Yoshizawa
  • Function : Author
Keisuke Sekine
  • Function : Author
Yoshikatsu Uematsu
  • Function : Author
Hisashi Murayama
  • Function : Author
Yumiko Nagai
  • Function : Author
Wojciech Krezel
  • Function : Author
Toshio Matsumoto
  • Function : Author
Shigeaki Kato
  • Function : Author


VDR forms heterodimers with one of three RXRs, RXRα, RXRβ, and RXRγ, and it is thought that RXR ligands can also modulate the trans-activation function of VDR/RXR heterodimers. In the present study we generated VDR/RXRγ double null mutant mice to examine the convergent actions of vitamin D and vitamin A signaling and to explore the possibility of a functionally redundant VDR. Although RXRγ−/− mice exhibited no overt abnormalities, VDR−/−/RXRγ−/− mice appeared similar to VDR−/− mice, showing features typical of vitamin D-dependent rickets type II, including growth retardation, impaired bone formation, hypocalcemia, and alopecia. However, compared to VDR−/− mice, growth plate development in VDR−/−/RXRγ−/− mutant mice was more severely impaired. Normalizing mineral ion homeostasis through dietary supplementation with high calcium and phosphorous effectively prevented rachitic abnormalities, except for disarranged growth plates in VDR−/−/RXRγ−/− mutant mice, and alopecia in both VDR−/− and VDR−/−/RXRγ−/− mutant mice. Histological analysis of VDR−/−/RXRγ−/− growth plates revealed that development of the hypertrophic chondrocytes was selectively impaired. Thus, our findings indicated that the combined actions of VDR- and RXRγ-mediated signals are essential for the normal development of growth plate chondrocytes, and raised the possibility that a functionally redundant VDR is present on chondrocytes as a heterodimer with RXRγ.

Dates and versions

hal-04094309 , version 1 (10-05-2023)



Naoko Yagishita, Yoko Yamamoto, Tatsuya Yoshizawa, Keisuke Sekine, Yoshikatsu Uematsu, et al.. Aberrant Growth Plate Development in VDR/RXRγ Double Null Mutant Mice. Endocrinology, 2001, 142 (12), pp.5332-5341. ⟨10.1210/endo.142.12.8544⟩. ⟨hal-04094309⟩
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