RRC ID 76437
Author Kise S, Iijima A, Nagao C, Okada T, Mano H, Nishikawa M, Ikushiro S, Kanemoto Y, Kato S, Nakanishi T, Sato S, Yasuda K, Sakaki T.
Title Functional analysis of vitamin D receptor (VDR) using adenovirus vector.
Journal J Steroid Biochem Mol Biol
Abstract Recently, we generated type II rickets model rats, including Vdr(R270L), Vdr(H301Q), Vdr(R270L/H301Q), and Vdr-knockout (KO), by genome editing. All generated animals showed symptoms of rickets, including growth retardation and abnormal bone formation. Among these, only Vdr-KO rats exhibited abnormal skin formation and alopecia. To elucidate the relationship between VDR function and rickets symptoms, each VDR was expressed in human HaCaT-VDR-KO cells using an adenovirus vector. We also constructed an adenovirus vector expressing VDR(V342M) corresponding to human VDR(V346M) which causes alopecia. We compared the nuclear translocation of VDRs after adding 1α,25-dihydroxyvitamin D3 (1,25D3) or 25-hydroxyvitamin D3 (25D3) at final concentrations of 10 and 100 nM, respectively. Both 25D3 and 1,25D3 induced the nuclear translocation of wild type VDR and VDR(V342M). Conversely, VDR(R270L) translocation was observed in the presence of 100 nM 25D3, with almost no translocation following treatment with 10 nM 1,25D3. VDR(R270L/H301Q) failed to undergo nuclear translocation. These results were consistent with their affinity for each ligand. Notably, VDR(R270L/H301Q) may exist in an unliganded form under physiological conditions, and factors interacting with VDR(R270L/H301Q) may be involved in the hair growth cycle. Thus, this novel system using an adenovirus vector could be valuable in elucidating vitamin D receptor functions.
Volume 230
Pages 106275
Published 2023-6-1
DOI 10.1016/j.jsbmb.2023.106275
PII S0960-0760(23)00030-4
PMID 36854350
MeSH Adenoviridae / genetics Alopecia / genetics Animals Calcifediol Humans Rats Receptors, Calcitriol* / genetics Rickets* Vitamin D / pharmacology
IF 3.813
DNA material pAxEFwtit2 (RDB05215)