A Humanized Mouse Model of Hereditary 1,25-Dihydroxyvitamin D–Resistant Rickets Without Alopecia

August 2014 in “ Endocrinology ”

Seong Min Lee, Joseph J. Goellner, Charles A. O’Brien, J. Wesley Pike

alopecia 1,25-dihydroxyvitamin D VDR hereditary 1,25-dihydroxyvitamin D-resistant rickets hVDR gene L233S mutation VDR-null mice dermal cysts hair loss vitamin D receptor HVDRR

Studysummary This study created a humanized mouse model of hereditary vitamin D-resistant rickets that lacks alopecia, indicating the mutant receptor's potential to explore the syndrome's characteristics beyond vitamin D binding. Our plain-language summary of this paper — not a Tressless recommendation.

In the 2014 study, researchers developed a humanized mouse model of hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) that does not exhibit alopecia, a common but not universal symptom of the disease. They achieved this by introducing a human VDR (hVDR) gene with a specific mutation (L233S) into VDR-null mice, which normally display both rickets and alopecia. The mutation in the hVDR gene prevented the binding of 1,25-dihydroxyvitamin D3, which is necessary for the activation of the VDR. While the mutant hVDR did not correct the systemic and skeletal abnormalities seen in VDR-null mice, it successfully prevented the development of alopecia and dermal cysts. This model allows for the study of HVDRR without the confounding factor of hair loss and can help identify new functions of the VDR that are independent of its role in vitamin D metabolism.

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research Mutations in the Vitamin D Receptor and Hereditary Vitamin D-Resistant Rickets

107 citations , March 2014 in “BoneKEy Reports”

This abstract reviews hereditary vitamin D-resistant rickets, a rare genetic condition causing severe early childhood rickets, and reports no new results; effective treatment typically requires high doses of calcium to address hypocalcemia and secondary hyperparathyroidism.

research Overexpression of Hedgehog Signaling Is Associated With Epidermal Tumor Formation in Vitamin D Receptor-Null Mice

100 citations , August 2011 in “Journal of Investigative Dermatology”

Lack of vitamin D receptor increases skin tumor risk by boosting hedgehog signaling.

research Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

1533 citations , October 2008 in “Endocrine reviews”

This research highlights that engineered mice lacking the vitamin D receptor show multiple health issues similar to human vitamin D deficiency, underscoring the widespread impacts of the vitamin D endocrine system.

research Inactivation of the Vitamin D Receptor Enhances Susceptibility of Murine Skin to UV-Induced Tumorigenesis

148 citations , May 2008 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that mice lacking the vitamin D receptor (VDR) developed skin tumors more rapidly than those with normal VDR activity, regardless of 1,25-dihydroxyvitamin D(3) presence.

research Hair Follicle Expression of 1,25-Dihydroxyvitamin D3 Receptors During the Murine Hair Cycle

95 citations , July 2006 in “British Journal of Dermatology”

This study observed that vitamin D receptor expression in certain hair follicle cells varies throughout the murine hair cycle, suggesting a potential role for 1,25-dihydroxyvitamin D3 in hair follicle biology.

research Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

78 citations , November 2005 in “Endocrinology”

This study found that Hairless (Hr) acts as a corepressor of the vitamin D receptor (VDR) in human keratinocytes, blocking the action of vitamin D on keratinocyte differentiation.

research Ligand-Independent Actions of the Vitamin D Receptor Maintain Hair Follicle Homeostasis

144 citations , December 2004 in “Molecular Endocrinology”

This study found that the effects of the vitamin D receptor on hair follicle cycling in mice are independent of its ability to bind a hormone, with specific domain mutations influencing hair regrowth outcomes.

research 25 Hydroxyvitamin D 1 Alpha-Hydroxylase Is Required for Optimal Epidermal Differentiation and Permeability Barrier Homeostasis

140 citations , April 2004 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that mice lacking the 1αOHase enzyme, which is responsible for producing a key vitamin D metabolite, showed impaired epidermal differentiation and delayed recovery of skin barrier function after disruption.

research Deletion of DNA Binding Domain of the Vitamin D Receptor Abrogates Genomic and Nongenomic Functions of Vitamin D

277 citations , July 2002 in “Molecular Endocrinology”

In this study, homozygous VDR null mutant mice exhibited nonfunctional vitamin D receptors, leading to growth abnormalities and revealing the limited physiological importance of vitamin D pathways outside the classical receptor.

Targeted Expression of Human Vitamin D Receptor in the Skin Promotes the Initiation of the Postnatal Hair Follicle Cycle and Rescues Alopecia in Vitamin D Receptor Null Mice

research Targeted Expression of Human Vitamin D Receptor in the Skin Promotes the Initiation of the Postnatal Hair Follicle Cycle and Rescues Alopecia in Vitamin D Receptor Null Mice

57 citations , April 2002 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that the vitamin D receptor is crucial for initiating the postnatal hair follicular cycle in mice, preventing alopecia associated with its inactivation.

research Targeting Expression of the Human Vitamin D Receptor to the Keratinocytes of Vitamin D Receptor Null Mice Prevents Alopecia

115 citations , December 2001 in “Endocrinology”

This study found that restoring vitamin D receptor expression specifically in the keratinocytes of VDR null mice prevented alopecia and enhanced hair follicle response during anagen initiation.

research Evaluation of Keratinocyte Proliferation and Differentiation in Vitamin D Receptor Knockout Mice

114 citations , June 2000 in “Endocrinology”

In this study, the researchers found that alopecia in VDR null mice is likely due to issues with hair cycle initiation rather than defects in keratinocyte proliferation or differentiation.