Normal vitamin D receptor function with increased expression of 25-hydroxyvitamin D(3)-24-hydroxylase in Corriedale sheep with inherited rickets.
A likely inherited disease with gross and microscopic features of rickets has been recognised in Corriedale sheep in New Zealand, and a defect in end-organ responsiveness to vitamin D has been proposed as a likely mechanism. The aim of the present study was to characterize the mode of inheritance and determine the disease mechanism. Breeding trials showed that the mode of inheritance was autosomal recessive. Serum chemistry testing using different methodology and studies in cultured skin fibroblasts did not support our previous hypothesis of a defect in end-organ responsiveness. The studies revealed normal serum 1,25-dihydroxyvitamin D concentrations, normal vitamin D receptor function, and the presence of 24-hydroxylase mRNA in cells from affected sheep, even without induction by 1,25-dihydroxyvitamin D(3). In addition, osteocalcin mRNA expression was similar in both affected and control sheep. It was concluded that increased expression of 25-hydroxyvitamin D(3)-24-hydroxylase, the enzyme that breaks down vitamin D, may be involved in the pathogenesis of inherited rickets in Corriedale sheep, but its role requires further clarification.
Dittmer
K E
KE
Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11 222, Palmerston North 4442, New Zealand. K.E.Dittmer@massey.ac.nz
Howe
L
L
Thompson
K G
KG
Stowell
K M
KM
Blair
H T
HT
Cockrem
J F
JF
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D012279:Rickets / Q000235:genetics / Q000662:veterinary*; D012756:Sheep; D012757:Sheep Diseases / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase