Co-expression of CYP27B1 enzyme with the 1.5kb CYP27B1 promoter-luciferase transgene in the mouse.
The renal enzyme 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1), responsible for the synthesis of circulating. 1,25-dihydroxyvitamin D (1,25D), is also expressed in a number of non-renal tissues. The regulation of CYP27B1 expression by the short flanking promoter outside the kidney is, however, largely unknown. We have used a transgenic mice expressing the 1.5kb promoter of the human CYP27B1 gene fused to the firefly luciferase gene in order to investigate tissue-specific CYP27B1 expression. These transgenic animals demonstrated co-localised luciferase and endogenous CYP27B1 expression in kidney proximal convoluted tubular cells. Strong co-expression of luciferase and CYP27B1 also occurred in neurons and Purkinje cells of the cerebellum and in Leydig and Sertoli cells of the testes. Other tissues to exhibit CYP27B1-promoter directed luciferase activity included lung, prostate, trabecular bone and jejunum as well as the choroid epithelium. The tissue specific changes in luciferase activity were age-related. These findings demonstrate that the proximal 1.5kb 5' flanking region of the CYP27B1 gene directs the expression of CYP27B1 in a number of known and novel tissues in a specific manner.
Anderson
Paul H
PH
Endocrine Research Laboratory, Hanson Institute, Frome Road, Adelaide 5000, SA, Australia. paul.anderson@imvs.sa.gov.au
Hendrix
Ivanka
I
Sawyer
Rebecca K
RK
Zarrinkalam
Reza
R
Manavis
Jim
J
Sarvestani
Ghafar T
GT
May
Brian K
BK
Morris
Howard A
HA
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D024506:5' Flanking Region; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D019076:Transgenes
D011993:Recombinant Fusion Proteins; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase