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Correction of the abnormal mineral ion homeostasis with a high-calcium, high-phosphorus, high-lactose diet rescues the PDDR phenotype of mice deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1).
Bone 2003; 32(4):332-40BONE

Abstract

Mutations in the 25-hydroxyvitamin D-1alpha-hydroxylase gene (CYP27B1; 1alpha-OHase) cause pseudo vitamin D deficiency rickets (PDDR), while mutations in the vitamin D receptor (VDR) cause hereditary vitamin D resistance rickets. Animal models of both diseases have been engineered. The bone phenotype of VDR-ablated mice can be completely rescued by feeding the animals with a high-calcium, high-phosphorus, high-lactose diet. We have attempted to rescue the PDDR phenotype of mice deficient for the 1alpha-OHase gene by feeding them with the high-calcium diet. The rescue regimen consisted of feeding a diet containing 2% calcium, 1.25% phosphorus, 20% lactose (rescue diet) from 3 weeks of age until sacrifice at 8.5 weeks of age. Blood biochemistry analysis revealed that the rescue diet corrected the hypocalcemia and secondary hyperparathyroidism. Despite the restoration of normocalcemia, 1alpha-OHase(-/-) (and 1alpha-OHase(+/-)) animals fed the rescue diet initially gained weight less rapidly than control mice fed normal mouse chow. Although 1alpha-OHase(-/-) mice fed the rescue diet eventually reached the same weight as control animals, the treatment did not entirely correct bone growth, as femur size remained significantly smaller than that of control. Bone histology and histomorphometry confirmed that the rickets and osteomalacia were cured. The rescue diet also restored the biomechanical properties of the bone tissue within normal parameters. These results demonstrate that correction of the abnormal mineral ion homeostasis by feeding with a high-calcium rescue diet is effective to rescue the PDDR phenotype of 1alpha-OHase mutant mice. This treatment, however, does not appear as effective as 1,25(OH)(2)D(3) replacement therapy since bone growth remained impaired.

Authors+Show Affiliations

Genetics Unit, Shriners Hospital for Children, Montreal, Quebec H3G 1A6, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12689675

Citation

Dardenne, O, et al. "Correction of the Abnormal Mineral Ion Homeostasis With a High-calcium, High-phosphorus, High-lactose Diet Rescues the PDDR Phenotype of Mice Deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1)." Bone, vol. 32, no. 4, 2003, pp. 332-40.
Dardenne O, Prud'homme J, Hacking SA, et al. Correction of the abnormal mineral ion homeostasis with a high-calcium, high-phosphorus, high-lactose diet rescues the PDDR phenotype of mice deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1). Bone. 2003;32(4):332-40.
Dardenne, O., Prud'homme, J., Hacking, S. A., Glorieux, F. H., & St-Arnaud, R. (2003). Correction of the abnormal mineral ion homeostasis with a high-calcium, high-phosphorus, high-lactose diet rescues the PDDR phenotype of mice deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1). Bone, 32(4), pp. 332-40.
Dardenne O, et al. Correction of the Abnormal Mineral Ion Homeostasis With a High-calcium, High-phosphorus, High-lactose Diet Rescues the PDDR Phenotype of Mice Deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1). Bone. 2003;32(4):332-40. PubMed PMID: 12689675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correction of the abnormal mineral ion homeostasis with a high-calcium, high-phosphorus, high-lactose diet rescues the PDDR phenotype of mice deficient for the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1). AU - Dardenne,O, AU - Prud'homme,J, AU - Hacking,S A, AU - Glorieux,F H, AU - St-Arnaud,R, PY - 2003/4/12/pubmed PY - 2003/12/12/medline PY - 2003/4/12/entrez SP - 332 EP - 40 JF - Bone JO - Bone VL - 32 IS - 4 N2 - Mutations in the 25-hydroxyvitamin D-1alpha-hydroxylase gene (CYP27B1; 1alpha-OHase) cause pseudo vitamin D deficiency rickets (PDDR), while mutations in the vitamin D receptor (VDR) cause hereditary vitamin D resistance rickets. Animal models of both diseases have been engineered. The bone phenotype of VDR-ablated mice can be completely rescued by feeding the animals with a high-calcium, high-phosphorus, high-lactose diet. We have attempted to rescue the PDDR phenotype of mice deficient for the 1alpha-OHase gene by feeding them with the high-calcium diet. The rescue regimen consisted of feeding a diet containing 2% calcium, 1.25% phosphorus, 20% lactose (rescue diet) from 3 weeks of age until sacrifice at 8.5 weeks of age. Blood biochemistry analysis revealed that the rescue diet corrected the hypocalcemia and secondary hyperparathyroidism. Despite the restoration of normocalcemia, 1alpha-OHase(-/-) (and 1alpha-OHase(+/-)) animals fed the rescue diet initially gained weight less rapidly than control mice fed normal mouse chow. Although 1alpha-OHase(-/-) mice fed the rescue diet eventually reached the same weight as control animals, the treatment did not entirely correct bone growth, as femur size remained significantly smaller than that of control. Bone histology and histomorphometry confirmed that the rickets and osteomalacia were cured. The rescue diet also restored the biomechanical properties of the bone tissue within normal parameters. These results demonstrate that correction of the abnormal mineral ion homeostasis by feeding with a high-calcium rescue diet is effective to rescue the PDDR phenotype of 1alpha-OHase mutant mice. This treatment, however, does not appear as effective as 1,25(OH)(2)D(3) replacement therapy since bone growth remained impaired. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/12689675/Correction_of_the_abnormal_mineral_ion_homeostasis_with_a_high_calcium_high_phosphorus_high_lactose_diet_rescues_the_PDDR_phenotype_of_mice_deficient_for_the_25_hydroxyvitamin_D_1alpha_hydroxylase__CYP27B1__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756328203000231 DB - PRIME DP - Unbound Medicine ER -