Normal vitamin D receptor function with increased expression of 25-hydroxyvitamin D3-24-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 D3. In addition, osteocalcin mRNA expression was similar in both affected and control sheep. It was concluded that increased expression of 25-hydroxyvitamin D3-24-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.